Pharmacokinetics Masterclass: Applications in Practice

Explore how bioavailability (F) determines how much oral drug reaches circulation, compare oral and IV AUC, adjust doses to match IV exposure through case studies.

Define clearance as the volume of plasma cleared of drug per unit time. Relate elimination rate and plasma concentration, and use AUC to guide maintenance and loading doses to steady-state.

Learn how half-life t½ governs dosing intervals and time to steady state using the elimination rate constant k and the 0.693/k rule, with first-order versus zero-order kinetics.

Explore pharmacokinetics case studies, calculating oral bioavailability from AUC with Bayes factor, and determining clearance, volume of distribution, and time to safe levels using half-lives.

Calculate the loading dose from target concentration and volume of distribution, adjusted for bioavailability and soft factor, to rapidly reach steady-state concentration for drugs with long half-lives.

Learn how to calculate the maintenance dose to sustain therapeutic levels, driven by clearance, dosing interval, and target concentration. The lecture also explains loading dose and the role of bioavailability.

Learn how time to steady state depends on half-life, not dose, reaching about 97% of css after 4–5 half-lives, with loading doses and monitoring guidance for narrow therapeutic index drugs.

Explore case studies on loading and maintenance dosing of antibiotics and antiseizure drugs, focusing on concentration-dependent killing, renal dosing adjustments, extended-interval aminoglycoside regimens, and practical dose calculations.

Learn the purpose and steps of therapeutic drug monitoring (TDM), including indications, when to apply, interpreting results, and how to adjust dosing to optimize efficacy and minimize toxicity.

Compare results to therapeutic ranges and free versus total drug levels, phenytoin and valproate. Use lab data with symptoms and renal and liver function to guide response and adjust dosing.

Adjust doses for renal impairment using creatinine clearance to prevent accumulation. Monitor hepatic impairment effects on phenytoin and theophylline; reduce doses for pediatric, geriatric, and critically ill patients in ICU.

Analyze the pharmacokinetics of special drugs, focusing on digoxin, and learn how absorption, distribution, metabolism, and renal function shape toxicity risk and therapeutic levels.

Explore lithium's narrow therapeutic index, maintenance and acute dose ranges, kidney-driven elimination, 12-hour post-dose monitoring, toxicity signs, and drug interactions that alter sodium and lithium levels.

Phenytoin shows saturable pharmacokinetics with zero-order kinetics after saturation; therapeutic range is 10–20 mcg/mL, free level 1–2 mcg/mL, and albumin binding affects levels, with toxicity causing ataxia, nystagmus, and confusion.

Theophylline pharmacokinetics encompass a 10–20 µg/mL target range and CYP1A2 metabolism. Smoking and age affect clearance; monitor levels during dose changes or illness to prevent toxicity like tremors, seizures, tachycardia.

Gentamicin requires troughs below 1 mcg/mL and peaks 5–10 mcg/mL with renal clearance and monitoring for nephrotoxicity; vancomycin uses troughs 15–20 mcg/mL and renal-adjusted dosing in critical illness.

Explore case studies to evaluate pharmacokinetic interactions such as carbamazepine's enzyme induction reducing valproate levels, carbamazepine autoinduction, and hepatic impairment's impact on clearance, guiding targeted dosing and monitoring.

Explore how renal impairment alters pharmacokinetics, including decreased clearance, longer half-life, shifts in volume of distribution and protein binding changes in uremia, with AKI vs CKD dosing and monitoring.

Explore case studies on adjusting drug doses for renal impairment using creatinine clearance, including gentamicin dose reduction to 55% of normal and digoxin dosing in CKD stage three.

Explore linear versus non-linear pharmacokinetics, illustrating saturation in metabolic processes, zero-order and first-order kinetics, and dose-concentration relationships with case studies on toxicity risks.

Compare concentration- dependent and time- dependent killing to guide dosing. Concentration- dependent killing requires Cmax 8–10× MIC and post-antibiotic effect, while time- dependent killing requires time above MIC.

Bayesian case studies on dose adjustments for kidney- and protein-binding–related pharmacokinetic changes, highlighting free phenytoin monitoring, gentamicin and vancomycin trough targets, theophylline toxicity, and carbamazepine autoinduction.