Glossary

The 500 dalton rule proposes that a compound must have a molecular weight below 500 daltons to cross the skin.

Absolute bioavailability, F measured against an intravenous dose.

Absorption is the movement of the drug from the site of administration into the blood.

Absorption is the movement of a drug from the place where it is given into the blood.

Some absorption enhancers, substances added to a formulation, open the junctions for a short time.

Accumulation is the amount of drug left in the body from earlier doses.

The accumulation ratio, R, is most often the AUC over one interval at steady state, divided by the AUC over the first interval.

The agreement of the model's predictions with their measured values gives the accuracy.

Acids are drugs that can give up a proton, a hydrogen ion, and become negatively charged.

A prodrug is a compound with little or no activity of its own. In the body, an enzyme or a chemical reaction converts it to the active compound, the active metabolite.

The activity score is the sum of the values of the two alleles.

Four processes determine what happens to an oral dose: absorption, distribution, metabolism and excretion. Together, these four processes are called ADME.

ADME is the absorption, distribution, metabolism and excretion of a drug.

To fill a full ADME profile for each compound. The profile is the set of ADME values that the projection needs.

Adsorbents, which bind the drug in the intestine, and other drugs, for example drugs that inhibit the efflux transporters, can interrupt the cycle.

Changes in the excretion of MPAG in urine and in the binding of MPA to albumin, a plasma protein, can also contribute.

An allele is one version of a gene, and each person carries two copies of most genes, one from each parent.

Each person inherits one version of most genes from each parent, and each version is an allele.

Allometry is the study of how a property of an animal changes with its body size. Allometric scaling uses this relation to predict human values from animal values.

Allometry is the study of how a property of an animal changes with its body size.

Anions are molecules with a negative charge.

Dabigatran is an anticoagulant, a drug that reduces the formation of blood clots.

Two studies of apixaban, an oral drug that reduces blood clotting, show both properties.

Apixaban, a drug that reduces blood clotting, shows the results of all five assays.

For an oral dose, the dose divided by this AUC is the apparent clearance, the clearance divided by the bioavailability.

The apparent permeability, Papp, is the rate at which drug appears on the far side, per unit of layer area and of initial concentration.

The applicability domain is the part of chemical space where the model predicts reliably.

The approved label, the official prescribing information, gives the maintenance dose for up to 5 days.

Clast, the last measured concentration, divided by lambda z is the area after the last sample.

The area under the curve, AUC, measures the exposure: the plasma concentration added up over time.

The area under the whole concentration-time curve, the AUC, measures the total exposure to the drug.

An assay is a laboratory test that measures one property of a drug.

The efflux transporters P-glycoprotein, or P-gp, and BCRP, the breast cancer resistance protein, pump drugs back into the lumen. They use energy from ATP, the molecule that stores energy in the cell.

P-glycoprotein, or P-gp, and breast cancer resistance protein, or BCRP, lie in the membrane that faces the blood. They use energy from ATP, adenosine triphosphate, the molecule that stores energy in cells.

The study measured the AUC, the area under the serum concentration-time curve.

The AUC is the area under the concentration-time curve, a measure of exposure.

Exposure describes the drug concentrations in the plasma after a dose. It is measured as the AUC, the area under the plasma concentration-time curve, and as the peak concentration, Cmax.

The AUMC is the area under the curve of time multiplied by concentration.

Balanced accuracy is the average of the two class fractions that a model predicts correctly.

Bases are drugs that can take up a proton and become positively charged.

Between-subject variability is the spread of the individual values around the typical value.

Bile is a fluid that the liver secretes into the small intestine.

Bile is a fluid that liver cells make, and biliary excretion is the transport of a drug or its metabolites into bile.

The membrane on the bile side faces the bile canaliculus, a small channel between adjacent hepatocytes that drains into the bile ducts.

Bile salts are detergent molecules in bile, and the gallbladder releases more bile into the duodenum after a meal.

An intravenous dose enters the systemic circulation directly. Its bioavailability, the fraction of the dose that reaches the systemic circulation unchanged, is 1, or 100 percent, by definition.

Bioavailability is the fraction of an oral dose that reaches the systemic circulation unchanged.

The ratio of the AUC after an oral dose to the AUC after an equal intravenous dose is the bioavailability, F.

Bioavailability, F, is the fraction of a dose that reaches the systemic circulation unchanged.

Two products are bioequivalent when their rate and extent of absorption agree within set limits.

A bioequivalence study compares two products of the same drug.

The Biopharmaceutics Classification System, or BCS, sorts drugs into four classes.

The Biopharmaceutics Classification System, or BCS, places a drug in one of four classes by its solubility and its permeability.

The study took biopsies, small tissue samples, from the duodenum.

The blood-brain barrier is the wall of the brain capillaries, the smallest blood vessels.

Organs receive very different shares of the blood that the heart pumps each minute, the cardiac output.

The central compartment is the plasma and the organs that the drug reaches fast, such as the liver.

Chemical space is the set of all possible structures, and a map of it places similar compounds close together.

Clearance is the volume of plasma from which the body removes all of the drug in a unit of time.

Clearance is the volume of plasma from which the body removes all of the drug per unit of time.

Clearance, CL, is the rate of elimination divided by the plasma concentration.

Clearance, CL, is the volume of plasma from which the body removes all of the drug per unit of time.

At steady state, when concentrations stay constant, Kp,uu equals the clearance into the brain divided by the clearance out of the brain. Each clearance is the volume of fluid from which all unbound drug is removed per unit time.

After an oral dose, the concentration rises while absorption is faster than elimination. It reaches a peak, Cmax, at the time tmax, and then falls.

The highest measured concentration is Cmax, and its time is tmax.

The coefficient, a, is the value of Y at 1 kilogram.

The coefficient of determination measures how closely the predictions follow the measured values, and 1 is perfect.

A cold pressor test is a pain test with the hand in ice water.

MPAG is the only form of the drug found in bile, so the cycle depends on bacteria in the colon, the large intestine.

A compartment is a space in which the drug concentration is the same everywhere at a given time.

Noncompartmental analysis. It uses no compartments, the spaces of uniform drug concentration in a model, and it makes few assumptions.

A confidence interval is the range that is likely to contain the true ratio.

A phase 2 reaction attaches a small molecule or group of atoms to a functional group. The product is a conjugate.

A conjugate forms when an enzyme joins a drug or metabolite to a polar group.

The core of a molecule is its ring systems and the chains that link them.

Covariates are measured patient factors, such as body weight or kidney function, that explain part of the between-subject variability.

Creatinine is a waste product of muscle, and its clearance is a measure of kidney function.

Clinicians estimate kidney function from creatinine, a waste product mainly from muscle.

Cytochrome P450 enzymes, or CYP enzymes, carry out most phase 1 oxidations.

Cytochrome P450 enzymes, or CYP enzymes, form a superfamily, a large group of proteins from genes with a common origin.

Phase 1 reactions add or expose a functional group, most often by oxidation. Cytochrome P450 enzymes, or CYPs, carry out most of these reactions.

The most common reaction is oxidation by cytochrome P450 enzymes, or CYPs.

Digoxin is a drug for heart failure and for atrial fibrillation, a fast and irregular heart rhythm.

The tablet swells and breaks into smaller particles; this step is called disintegration.

Dissolution is the process in which molecules leave the solid drug and enter the fluid.

The dissolution rate is the mass of drug that dissolves in a unit of time.

Distribution is the movement of the drug from the blood into the tissues.

Distribution is the reversible movement of a drug from the blood into the tissues and back.

The distribution phase is the early, fast fall of the plasma concentration, while drug moves into the peripheral compartment.

The AUC of one dose equals F times the dose, divided by CL. Solved for the dose, this gives the dose equation: the dose equals CL times the target AUC, divided by F.

In linear pharmacokinetics, the parameters stay the same at every dose. Exposure then rises in proportion to the dose. This property is dose proportionality.

The dose rate is the dose divided by the interval between doses.

The dosing interval is the time from one dose to the next.

The model also predicts drug interactions, the changes in exposure to one drug that a second drug causes.

Drug parameters describe the drug, for example its solubility in water and fat, its charge, its binding to plasma proteins and its rate of metabolism.

In the duodenum, the first part of the small intestine, the median pH is 6.1.

The duodenum is the first part of the small intestine.

A duplication places extra gene copies in one allele.

Efflux is the transport of drug out of the cells, back toward the gut.

The efflux ratio is Papp from the blood side to the gut side, divided by Papp in the reverse direction.

Efflux transporters are proteins that carry their substrates, the molecules they transport, out of a cell.

Efflux transporters, such as P-glycoprotein, or P-gp, are membrane proteins that pump drugs out and can lower absorption.

Metabolism and excretion together are called elimination.

Elimination is the irreversible loss of the drug from the body, by metabolism or by excretion in urine or bile.

The elimination phase is the later, slow fall, in which the plasma and tissue concentrations fall in parallel.

The rate divided by the amount is the elimination rate constant, k.

The elimination rate constant, k, is the rate of elimination divided by the amount.

An endpoint is the measured property.

The cells on each villus, the enterocytes, carry microvilli on their surface.

The inner surface of the gut wall faces the lumen, the space inside the gut. This surface is a single layer of cells, and most of them are enterocytes, the cells that absorb nutrients and drugs.

Part of the drug can be reabsorbed from the gut and return to the liver; this is enterohepatic circulation.

The intestine absorbs the parent drug again, and the portal vein carries it from the intestine to the liver. This cycle of biliary excretion and intestinal reabsorption is enterohepatic recycling.

Enzyme inducers, drugs that increase the amount of an enzyme, raise the content.

Excretion is the removal of the drug and its metabolites from the body, mainly in urine and in bile.

Excretion removes the drug and its metabolites from the body.

The exponent, b, sets how fast Y changes with body weight.

Exposure is the plasma concentration of a drug added up over time.

Exposure describes the drug concentrations in the plasma after a dose.

The extended-release tablet, which releases the drug over many hours.

Fg and Fh each equal 1 minus the extraction ratio, the fraction of the drug that enters an organ and that the organ removes.

The extraction ratio is the fraction of the drug that enters the liver and that the liver removes in one pass of the blood.

Fa, the fraction absorbed, is the fraction of the dose that crosses into the gut wall.

In the gut and the kidney, the endothelial cells have pores called fenestrae.

Fetal Kp,uu is the unbound drug concentration in fetal plasma divided by that in maternal plasma.

Fg is the fraction of the absorbed drug that escapes metabolism in the gut wall.

Fg is the fraction of this drug that escapes metabolism in the gut wall.

Fh is the fraction of the drug that passes through the liver unchanged.

Fh is the fraction of the drug that enters the liver and escapes removal there, mainly by metabolism.

A fingerprint is a row of bits, and the bits record which small substructures the molecule contains.

In first-order elimination, the rate of elimination, the amount removed per unit of time, is proportional to the amount of drug in the body.

Enzymes in both organs can metabolize the drug, that is, change it chemically into other compounds. The most common reaction is oxidation by cytochrome P450 enzymes, or CYPs. This loss of drug in the gut wall and the liver, on this first pass through the two organs, is first-pass metabolism.

Fixed effects have one value for all patients, such as the typical clearance.

Fluctuation, the change of the concentration within one interval.

The fold error is the predicted clearance divided by the observed clearance.

A food effect is a change in exposure when a person takes a dose with a meal instead of in the fasted state.

The formulation is the product that holds the drug, for example a solution, a patch or an extended-release tablet.

The fraction of the dose that crosses from the gut lumen into the gut wall is called the fraction absorbed, Fa.

The fraction of the dose that enters the enterocytes is the fraction absorbed, Fa.

The fraction unbound, fu, is the unbound concentration divided by the total concentration, bound plus unbound.

The fraction unbound, fu, is the unbound drug concentration in plasma, the liquid part of the blood, divided by the total concentration.

Gastric emptying, the passage of stomach contents into the small intestine.

A gene, a section of DNA, holds the code for a protein, such as an enzyme.

The pair of alleles is the genotype.

The geometric mean of the fold errors, an average on a log scale, shows whether the predictions are too low or too high.

The glomerular filtration rate, GFR, is the volume of plasma that passes from the glomeruli into Bowman's space per unit of time.

Each nephron starts with a filter, the glomerulus, and continues as a tubule, where the filtered fluid becomes urine.

Each nephron starts at a glomerulus, a network of small blood vessels inside a capsule.

For example, glucuronic acid, a sugar acid, gives a glucuronide, an anion about 176 daltons heavier than the drug.

Glutathione, a small peptide, binds NAPQI and makes it harmless.

After removal of the patch, absorption continued, probably from a store of drug in the skin. The half-life, the time for the serum concentration to fall by one half, was therefore 17 hours.

Compared with placebo, rifampicin lowered the midazolam AUC by 96 percent and the peak concentration by 94 percent. The half-life, the time in which the plasma concentration falls by half, fell from 3.1 to 1.3 hours.

The half-life in the assay is the time in which half of the compound disappears.

Each CYP enzyme has a heme group, a ring structure with an iron atom at its center.

Hepatic blood flow, the volume of blood that passes through the liver per unit of time.

Hepatic blood flow is the upper limit of hepatic clearance.

Hepatic clearance is the clearance by the liver.

The liver removes drug by metabolism and by excretion into bile, and its clearance is the hepatic clearance.

Uptake into the hepatocyte, the liver cell that makes bile.

Hepatocytes are intact liver cells with all the enzymes that metabolize drugs, and their cofactors.

A high-extraction drug, for which the product of the unbound fraction and intrinsic clearance is much larger than hepatic blood flow.

A drug is highly soluble when its highest single dose is completely soluble in 250 milliliters or less of water-based fluid.

Hydrolysis, the third type, uses water to split a bond.

In hydrolysis, water splits a chemical bond.

Hydrophilic drugs dissolve well in water.

The IC50 is the concentration of the new drug that halves the probe drug metabolism in microsomes.

Mycophenolate mofetil shows how recycling and a second drug change the plasma concentration over time. It is an immunosuppressant, a drug that reduces the immune response, for example against a transplanted organ.

In vitro means in the laboratory, outside the body.

In vitro means outside a live organism, for example in a test tube.

In vitro intrinsic clearance, CLint, is the rate of metabolism in the assay divided by the drug concentration.

In vivo means inside a live organism.

An inducer is a substance that raises the amount of an enzyme.

An inhibitor lowers the activity of an enzyme, and an inducer raises the amount of the enzyme.

The infant dose is the milk concentration times the daily milk intake per kilogram of infant weight.

An inhibitor is a substance that lowers the activity of an enzyme.

An inhibitor is a drug that lowers the activity of an enzyme.

An intravenous bolus is a single dose injected into a vein over a short time.

Clearance is measured in each species after an intravenous dose, an injection into a vein.

Intrinsic clearance, the rate of metabolism in the liver divided by the unbound drug concentration at the enzymes.

Intrinsic clearance is the rate of metabolism divided by the unbound drug concentration at the enzymes.

The intrinsic clearance, CLint, measures the activity of the liver enzymes on unbound drug.

The charged form crosses the membrane only slowly, so the drug collects inside, a process called ion trapping.

IVIVE, in vitro to in vivo extrapolation, predicts a value in the body from a measurement in vitro.

Kp is the total brain concentration, bound plus unbound, divided by the total concentration in plasma, the liquid part of the blood.

If no transporter protein carries the drug and the pH is the same on both sides, the unbound concentrations become equal. The ratio of the unbound tissue concentration to the unbound plasma concentration is Kp,uu, and it is then 1.

Without a membrane transporter, the unbound concentrations in tissue and plasma are equal at steady state, when the concentrations stay constant. The ratio of the unbound tissue concentration to the unbound plasma concentration is Kp,uu, and it is then 1.

Lactic acidosis, an excess of lactic acid in the blood, is a rare adverse effect, and low metformin concentrations minimize its risk.

In linear pharmacokinetics, the parameters stay the same at every dose.

The linear-up/log-down method uses straight lines where the concentration increases, and straight lines on a logarithmic scale where it decreases.

Diazepam is lipophilic, or fat-soluble, and lipophilic drugs distribute well into adipose tissue, or body fat.

A lipophilic drug dissolves well in fat.

Drugs that dissolve well in fat are called lipophilic.

Lipophilic drugs, which dissolve better in fat than in water, dissolve in this core.

Lipophilicity, the tendency to dissolve in lipids, mainly sets the rate, because cell membranes are made of lipids.

Liver microsomes are fragments of the endoplasmic reticulum, a membrane network inside liver cells.

Liver microsomes are vesicles formed from the internal membranes of liver cells, and these membranes hold the cytochrome P450 enzymes.

A loading dose is a first dose, larger than the maintenance dose, that brings the plasma concentration to the target sooner.

Log P, the logarithm of the ratio of drug concentrations in octanol and water, measures lipophilicity.

A low-clearance drug has a liver clearance much smaller than the liver blood flow.

A low-extraction drug, for which that product is much smaller than hepatic blood flow.

The inner surface of the gut wall faces the lumen, the space inside the gut.

The lymph is a fluid that lymph vessels collect from the tissues and return to the blood near the heart.

Lysosomes are small acidic compartments inside cells.

Machine learning is a computer method that learns from examples the relation between a chemical structure and a measured ADME value.

A maintenance dose is a dose given at regular intervals, for example once a day, to keep the concentration near the target.

The mean residence time, MRT, is the AUMC divided by the AUC.

At each time, the median is the middle of the women's concentrations when they are put in order.

Metabolic stability, the resistance of a drug to metabolism.

Metabolism is the chemical change of the drug by enzymes, mainly in the liver.

Metabolism is the chemical change of a drug by enzymes, mainly in the liver.

Metabolism is the chemical change of the drug by enzymes, and excretion is its removal, mainly in urine and bile.

Metabolism is the chemical change of a drug by enzymes, proteins that make chemical reactions faster. The product is a metabolite.

Metabolism is the chemical change of a drug by enzymes, proteins that make chemical reactions faster. Its product is a metabolite.

Metabolites are the products that enzymes make from a drug.

Bile salts and lipids form micelles, small clusters with a lipid core.

Microsomes are small vesicles made from the endoplasmic reticulum, a membrane system inside liver cells.

The milk-to-plasma ratio is the drug concentration in milk divided by that in maternal plasma.

Molecular descriptors are numbers calculated from the structure, such as the molecular weight and the polar surface area. A fingerprint is a row of bits, and the bits record which small substructures the molecule contains. The model is the fitted relation between these numbers and the measured value.

Molecular descriptors are numbers calculated from the structure, such as the molecular weight and the polar surface area.

Each kidney contains many small units called nephrons.

Each kidney forms urine in many small units, the nephrons.

Noncompartmental analysis, or NCA, calculates each person's parameters, such as the AUC and the clearance, from that person's points.

Noncompartmental analysis, or NCA, calculates the parameters of a drug from the plasma concentrations of one person at set times.

Nonlinear means that the concentration is a curved function of the parameters, such as an exponential, even when clearance stays the same at every dose.

In nonlinear pharmacokinetics, at least one parameter changes with the dose.

Nonrenal clearance is the total clearance minus the renal clearance.

A normal metabolizer has normal activity, and an ultrarapid metabolizer has increased activity from extra gene copies or increased-function alleles.

A one-compartment model treats the body as one well-mixed space.

Loperamide is an opioid, a drug that acts on the same receptors as morphine.

Oral bioavailability is the fraction of the dose that reaches the systemic circulation unchanged, after the drug passes through the gut wall and the liver.

Oral bioavailability is the fraction of the dose that reaches the systemic circulation unchanged, after the drug passes through the gut wall and the liver.

The oral bioavailability, F, is the fraction of the dose that reaches the systemic circulation unchanged.

Oral bioavailability, F, is the fraction of the dose that reaches the systemic circulation unchanged.

Organic anions, with a negative charge, enter the tubule cells from the blood through OAT1 and OAT3.

Organic cations, with a positive charge, enter from the blood through OCT2, and MATE1 and MATE2-K move them into the tubule fluid.

Oxidation removes electrons from a molecule and often adds an oxygen atom.

An oxidation usually adds an oxygen atom to a molecule.

The efflux transporters P-glycoprotein, or P-gp, and BCRP, the breast cancer resistance protein, pump drugs back into the lumen.

Between the cells, the paracellular route.

Parameters are the values of a pharmacokinetic model, such as clearance.

Bile carries the drug or its conjugate into the intestine. There, gut bacteria can hydrolyze a conjugate back into the parent drug, the drug before conjugation.

Tight junctions close the gaps between the endothelial cells, so a drug must cross the cells. It can cross by passive diffusion, movement from a higher to a lower concentration without energy use.

Passive diffusion is movement from a higher to a lower concentration, without energy use.

A physiologically based pharmacokinetic model, or PBPK model, makes each compartment a real organ or tissue, with the volume and blood flow of that organ.

After each dose, the plasma concentration rises to a peak, the highest concentration in the interval.

Fluctuation, the change of the concentration within one interval. The peak-to-trough ratio, the peak divided by the trough, measures it.

The peripheral compartment is the tissues that the drug reaches more slowly.

Permeability is the rate at which a drug crosses a barrier for each unit of area and each unit of concentration difference.

Permeability is the rate at which a drug crosses the gut wall.

The pH-partition hypothesis assumes that only the neutral form crosses the membrane.

Pharmacogenetics studies how inherited DNA differences change drug response.

A pharmacokinetic model is a set of equations that describes how the drug concentration changes with time.

A pharmacokinetic model is a set of equations for the drug concentration over time, with fixed numbers called parameters.

Pharmacokinetics describes what the body does to a drug.

Pharmacokinetics describes what the body does to a drug.

A phase 1 reaction adds or exposes a functional group, a small group of atoms to which phase 2 can attach a molecule.

Phase 1 reactions add or expose a functional group, most often by oxidation.

A phase 2 reaction attaches a small molecule or group of atoms to a functional group.

Phase 2 enzymes are mainly transferases, which move a group from a donor molecule to the drug.

Phase 2 reactions join the drug, or its phase 1 metabolite, to an endogenous molecule, such as glucuronic acid, sulfate or glutathione.

Transporters, proteins in the cell membrane that carry molecules across it, move the conjugate out of the liver cell. They move it into the bile, or into the blood for excretion in urine. Some authors call this transport step phase 3.

The phenotype is the enzyme activity of a person, and the genotype predicts it.

In tissue, many drugs bind mainly to phospholipids, the fat-like molecules that form cell membranes.

Distribution into tissues, where drugs also bind, mainly to phospholipids, the lipids of cell membranes, and to tissue proteins.

The pKa is the pH at which half of the molecules carry a charge.

For a drug with one ionizable group, the pKa is the pH at which half of its molecules carry a charge.

Plasma is the liquid part of the blood.

Plasma is the liquid part of the blood.

Platelets are small cell fragments in the blood.

Of the four main groups, a poor metabolizer has little or no activity, and an intermediate metabolizer has decreased activity.

Population pharmacokinetics, or population PK, fits one model to the data of all patients and explains part of the differences between them.

A positive food effect increases the exposure, and a negative food effect decreases it.

When a dissolved weak base moves from the stomach into the small intestine, part of it can precipitate, that is, form a solid again.

A probe drug is a drug that mainly one CYP metabolizes.

A prodrug has little or no activity until the body converts it into the active drug.

A prodrug is a compound with little or no activity of its own.

A projected human dose is the dose that a compound is predicted to need in patients, before anyone takes it.

Warfarin lengthens the prothrombin time, the time that plasma takes to clot in a test.

The first part of the tubule is the proximal tubule.

Random effects describe how far each patient differs from the typical value.

A random split takes the test compounds at random.

The rate of elimination, the amount of drug that the body removes per unit of time, equals the clearance times the plasma concentration.

The rate of elimination is the amount of drug that the body removes per unit of time.

Reabsorption, the movement of drug from the tubule fluid back into the blood.

Reduction, the second type, adds electrons to a molecule.

Relative bioavailability. It compares two products of the same drug, or two ways of giving it, without an intravenous dose.

The infant dose is the milk concentration times the daily milk intake per kilogram of infant weight. The relative infant dose is this dose as a percentage of the daily maternal dose per kilogram of maternal weight.

The kidneys excrete unchanged drug into urine, and their clearance is the renal clearance.

Renal clearance is the volume of plasma from which the kidneys remove all of the drug per unit of time.

Residual variability is the scatter of the measured points around the model curve of each patient.

The route of administration is the place where a dose enters the body.

A salt is the charged drug paired with a counter-ion, an ion of opposite charge.

Enzymes, the proteins that make chemical reactions faster, and transport proteins, which carry drugs across cell membranes, have a limited number of binding sites. Saturation is the condition in which most of these sites are occupied, so the rate rises little when the concentration rises.

A scaffold split holds back whole cores.

Secretion, the transport of drug from the blood into the fluid of the proximal tubule.

Serum is the liquid part of clotted blood.

In the liver, the capillaries, called sinusoids, have large openings, so even large molecules reach the liver cells.

Solubility is the concentration of dissolved drug when the fluid is in equilibrium with the solid drug.

Population PK works with sparse sampling, a few samples from each patient at different times, because it estimates the curve from all patients together.

The longer half-life delays steady state, the condition in which the dose rate equals the rate of elimination.

The peaks and troughs approach a level at which each dose replaces the drug eliminated in one interval. This condition is called steady state.

The stratum corneum, the thin outermost layer of dead cells in the skin, is the main barrier.

A subcutaneous injection places the drug in the tissue under the skin, and an intramuscular injection places it in a muscle.

The molecule that an enzyme converts is its substrate.

A continuous layer of fused cells, the syncytiotrophoblast, is the main barrier between the maternal blood and the fetus, the unborn child.

System parameters describe the body: organ volumes, blood flows, tissue composition and enzyme amounts.

The target exposure is the drug concentration in plasma over time that gives the required effect. Here it is the target AUC, the area under the curve of plasma concentration against time.

A target concentration is a plasma concentration chosen to be effective and safe.

The target exposure is the drug concentration in plasma over time that gives the required effect.

In 12 volunteers, the substrate was injected during an infusion of tariquidar, a drug that blocks P-gp, into a vein.

The terminal half-life is the time for the plasma concentration to fall by half after distribution is complete.

The terminal half-life. It is the half-life of the elimination phase, and it equals 0.693, the natural logarithm of 2, divided by beta.

The terminal phase, the last phase of the curve, and its rate constant, lambda z.

A test set is a group of compounds that the model does not learn from.

The number e, about 2.718, is the base of the natural logarithm.

Tight junctions, bands of protein near the lumen side of the cells, close the gaps between adjacent enterocytes.

A time split trains on the compounds measured before a date and tests on the later ones.

The tissue-to-plasma partition coefficient, Kp, is the total drug concentration in a tissue divided by the total concentration in plasma, when both are constant.

The total clearance is the clearance calculated from the total plasma concentration, bound plus unbound.

The training data are the compounds with measured values.

A drug can cross the gut wall by three main routes. The first is passive diffusion through the cells, the transcellular route.

Clearance depends on the blood flow to the liver and the kidneys and on their enzymes. It also depends on their transport proteins, proteins in the cell membrane that move the drug into or out of the cell.

The third route uses transporters, proteins in the cell membrane that carry nutrients and other natural substances.

Transporters, proteins in the cell membrane that carry molecules across it, move the conjugate out of the liver cell.

The trapezoidal rule adds the areas under straight lines between consecutive points.

After each dose, the plasma concentration rises to a peak, the highest concentration in the interval. It then falls to a trough, the lowest concentration, just before the next dose.

Lipophilic drug in the tubule can diffuse back into the blood, which is tubular reabsorption.

A two-compartment model describes the body as two spaces, and drug moves between them in both directions.

Phase 2 reactions join the drug, or its phase 1 metabolite, to an endogenous molecule, such as glucuronic acid, sulfate or glutathione. UDP-glucuronosyltransferases, or UGTs, sulfotransferases and glutathione S-transferases carry out these reactions.

Unbound drug is free in solution, not attached to proteins or membranes.

The unbound fraction is the fraction of drug in plasma not bound to proteins.

The unbound fraction is the unbound concentration divided by the total concentration.

The unbound fraction in blood, the concentration of drug that is not bound to proteins, divided by the total concentration in blood.

A variant, a difference in the DNA of an allele, can remove, lower, keep or raise the allele function.

The small intestine is about two thirds of the five-meter length of the gut, and its contents take about three hours to pass through it. Its inner lining forms circular folds, and the folds carry small projections called villi.

The volume of distribution is the amount of drug in the body divided by the plasma concentration.

The volume of distribution, Vd, is the amount of drug in the body divided by the plasma concentration, after distribution is complete.

The volume of distribution, Vd, is the amount of drug in the body divided by the plasma concentration.

Vss, the volume of distribution at steady state, is CL multiplied by MRT when the clearance is the same at every dose.

Vz, the volume of distribution in the terminal phase, is the clearance divided by lambda z.

This short rise lowers the solubility of some weak bases, drugs that dissolve better in acid than at a neutral pH.

A prediction is within twofold when the fold error lies between 0.5 and 2, and the fraction within twofold measures accuracy.