Professor of Veterinary Pharmacotherapy and Pharmacy Bioavailability Plasma Protein Binding and Volume of Distribution 18082021 Bioavailability 18082021 Pharmacodynamics ID: 1026487
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1. 18-08-2021Ronette GehringProfessor of Veterinary Pharmacotherapy and PharmacyBioavailability, Plasma Protein Binding, and Volume of Distribution
2. 18-08-2021Bioavailability
3. 18-08-2021PharmacodynamicsPharmacokineticsExtravascular doseToxicityUtilityEfficacyIntravenous doseAbsorptionMetabolismExcretionBloodTissueUnboundBoundBoundUnboundMeasurement
4. Bioavailability% of administered dose absorbed and can be measured in the central circulation% of dose reaching the biophase (site of action)18-08-2021
5. Bioavailability (F)Intravascular administration (IV)100%F=1Extravascular administrationSubcutaneous and intramuscular injectionF~1Oral and transdermalF<118-08-2021
6. Overall exposure 18-08-2021AUC
7. 18-08-2021Dose adjusments are needed when there are changes to bioavailability and clearance
8. Factors influencing bioavailabilityFormulationRoute of administrationFoodDiarrhoeaConstipationConcomitant medicationsPregnancy
9. CYP450 UDP-GTGut wallSystemic circulationBiotransformation(gut) &First pass effect CYP450 UDP-GTFaecesliverV. portae
10. Assessment of bioavailability Source: https://basicmedicalkey.com/drug-absorption-and-bioavailability/
11. Plasma protein binding
12. 18-08-2021PharmacodynamicsPharmacokineticsExtravascular doseToxicityUtilityEfficacyIntravenous doseAbsorptionMetabolismExcretionBloodTissueUnboundBoundBoundUnboundMeasurement
13. What are you measuring?Unbound or total plasma drug concentrations?-D-D-D-D-D-D-D-D-D-D-D-D-D-D-D-D-D-D-D-D-D-D-D-D-D-D-D-D-D-D-D-D
14. Plasma protein bindingAlbumenα-acid glycoproteinOthersSpeciesDiseaseInteractionsReproductive statusOften non-linear Dosing rateUnbound clearance[Binding sites]Affinity D-PCu
15. ConclusionsPharmacokinetic studies should ideally measure free drugTotal drug concentrations can overestimate efficacy when related to MIC valuesCorrecting based on in vitro plasma protein binding helps, but is not ideal