Pharmacokinetic Parameters

allelipraise's version from 2017-10-25 13:25

Section 1

Question Answer
Bioavailabilitymeasurement of both the rate of drug absorption and total amount of drug that reaches the general circulation from an administered dosage form
Amount of Drug AbsorbedBioavailability Factor, F, fraction of administered dose that was absorbed
Amount of Drug Absorbed π‘«π’“π’–π’ˆ 𝒂𝒃𝒔𝒐𝒓𝒃𝒆𝒅 = 𝑭 𝒙 𝒅𝒐𝒔𝒆
Equivalent DoseEquivalent doses of a drug is used when different dosage forms and/or strengths are used.
Equivalent Doseπ‘«π’π’”π’†π’π’†π’˜ 𝒅𝒇 𝒙 π‘­π’π’†π’˜ 𝒅𝒇 = 𝑫𝒐𝒔𝒆𝒐𝒍𝒅 𝒅𝒇 𝒙 𝑭𝒐𝒍𝒅 𝒅𝒇
Amount of Drug Absorbed from a Salt or Ester FormWhen a salt or ester of a drug is administered, F is multiplied by the fraction of the total molecular weight which the active drug represents (S). For the parent form, S = 1.0
Amount of Drug Absorbed from a Salt or Ester Formπ‘«π’“π’–π’ˆπ’‚π’ƒπ’”π’π’“π’ƒπ’†π’… = 𝑺𝒙𝑭𝒙𝑫𝒐𝒔𝒆
Plasma Drug Concentration Time Curve / Cumulative Urinary Drug Excretion CurveMethods of Bioavailability Assessment
Cumulative Urinary Drug Excretion CurveMeasurement of the concentration of the intact drug and its metabolite in the urine
AUCsimple numeric estimation of the extent of absorption of a drug from a product
AUCfor calculating the relative efficiency of different drug products
𝑨𝒃𝒔𝒐𝒍𝒖𝒕𝒆 π‘©π’Šπ’π’‚π’—π’‚π’Šπ’π’‚π’ƒπ’Šπ’π’Šπ’•π’šπ‘¨π’ƒπ’”π’π’π’–π’•π’† π‘©π’Šπ’π’‚π’—π’‚π’Šπ’π’‚π’ƒπ’Šπ’π’Šπ’•π’š = 𝑭 𝒂𝒃𝒔 𝐀𝐔𝐂𝒕𝒆𝒔𝒕 = πƒπ¨π¬πžπ’•π’†π’”π’• 𝐀𝐔𝐂𝑰𝑽 πƒπ¨π¬πžπ‘°π‘½
π‘Ήπ’†π’π’‚π’•π’Šπ’—π’† π‘©π’Šπ’π’‚π’—π’‚π’Šπ’π’‚π’ƒπ’Šπ’π’Šπ’•π’šπ‘Ήπ’†π’π’‚π’•π’Šπ’—π’† π‘©π’Šπ’π’‚π’—π’‚π’Šπ’π’‚π’ƒπ’Šπ’π’Šπ’•π’š = 𝑭 = 𝒓𝒆𝒍=𝐀𝐔𝐂𝒕𝒆𝒔𝒕 πƒπ¨π¬πžπ’•π’†π’”π’• 𝐀𝐔𝐂𝒓𝒆𝒇𝒆𝒓𝒆𝒏𝒄𝒆 πƒπ¨π¬πžπ’“π’†π’‡π’†π’“π’†π’π’„π’†
Pharmaceutical Equivalentsβ€’ same active ingredient(s) β€’ same dosage form and route of administration β€’ they are identical in strength or concentration
Pharmaceutical Alternativessame therapeutic moiety, but are different salts, esters, or complexes of that moiety, or are different dosage forms or strengths
Therapeutic Equivalentspharmaceutical equivalents that have the same clinical effect and safety profile when administered to patients
BA & BE Studiesevaluate the clinical efficacy of different dosage forms or products made by different manufacturers
selection of the same drug based on economic factorBA & BE Studies Benefits

Section 2

Question Answer
healthy; informed consent; confirm medical stateTesting on Humans: Health
18 to 40 yearsTesting on Humans: Age
Normal weightsTesting on Humans: Weight
nonsmokers; not taking certain other drugsTesting on Humans: Enzyme Status
10-20 subjectsTesting on Humans: Number
same method; sensitive and specificTesting on Humans: Assay
complete crossover; with a washout periodTesting on Humans: Design

Section 3

Question Answer
Clinical studiesDifferent products produce different therapeutic results
BA/BE studiesDifferent products are not bioequivalent
Basis of BE RequirementDrug has a narrow therapeutic range
Basis of BE RequirementLow solubility and/or large dose
Basis of BE RequirementPoor bioavailability
provides a prediction of in vivo pharmacokinetics of oral immediate release (IR) drug products by classifying drug compounds based on their solubility related to dose and intestinal permeability in combination with the dissolution properties of the dosage formBiopharmaceutics Classification System (BCS)

Section 4

Question Answer
HIGHLY SOLUBLEhighest strength is soluble < 250 ml water over a pH range of 1 to 7.5.
HIGHLY PERMEABLEextent of absorption > 90% of an administered dose in humans, based on mass balance or in comparison to an intravenous reference dose.
RAPIDLY DISSOLVING > 85% of the labeled amount of drug substance dissolves within 30 minutes using USP apparatus I or II in a volume of < 900 ml buffer solutions.

Section 5

Question Answer
Class I Drugsexhibit a high absorption number and a high dissolution number Rate-limiting step is drug dissolution
Metoprolol, Diltiazem, Verapamil, PropranololClass I drug Examples
β€’ β€’ β€’ Class II Drugsabsorption for class II drugs is usually slower than class I and occurs over a longer period of time
β€’ β€’ β€’ Class II DrugsIn vivo drug dissolution is the rate limiting step for absorption except at a very high dose number
β€’ β€’ β€’ Class II Drugsbsorption for class II drugs is usually slower than class I and occurs over a longer period of time systems developed for class II drug
β€’ β€’ β€’ β€’ β€’ micronization lyophilization addition of surfactants formulation as emulsions and microemulsion systems use of complexing agents like cyclodextrins class II drugs are based on
Phenytoin, Danazol, Ketoconazole, Mefenamic acid, NifedipineClass II drug Examples
Class III Drugspermeability is rate limiting step for drug absorption
Class III Drugsexhibit a high variation in the rate and extent of drug absorption
Class III Drugsrequire technologies that address fundamental limitations of absolute or regional permeability
Cimetidine, Acyclovir, Neomycin B, Captopril, Peptides and proteinsclass III drugs are based on
Class IV Drugsroute of choice: parenteral with the aid of solubility enhancers
Class IV Drugsexhibit a lot of problems for effective oral administration
Taxolclass IV drugs are based on
Biopharmaceutics Drug Disposition Classification System (BDDCS) a modified version of BCS
Biopharmaceutics Drug Disposition Classification System (BDDCS)useful in predicting overall drug disposition, including routes of drug elimination and the effects of efflux and absorptive transporters on oral drug absorption; when transporter-enzyme interplay will yield clinically significant effects (e.g., low bioavailability and drug-drug interactions); the direction, mechanism, and importance of food effects; and transporter effects on post absorption systemic drug concentrations following oral and intravenous dosing
Biopharmaceutics Drug Disposition Classification System (BDDCS) well supported by experimental data on the effect of transporter inhibition and induction on drug metabolism.
Biopharmaceutics Drug Disposition Classification System (BDDCS)uses elimination criteria, may expand the number of class 1 drugs eligible for a waiver of in vivo bioequivalence studies and provide predictability of drug disposition profiles for classes 2, 3, and 4 compounds.