Biopharmaceutics and Pharmacokinetics PDF

SAINT LOUIS UNIVERSITY DEPARTMENT OF PHARMACY PHARM 314: Biopharmaceutics and Pharmacokinetics UNIT 1 INTRODUCTION to Biopharmaceutics and Pharmacokinetics Compiled by: Cristopherson P. Mata, RPh, MS Pharm Sources: Towzer and...

SAINT LOUIS UNIVERSITY DEPARTMENT OF PHARMACY PHARM 314: Biopharmaceutics and Pharmacokinetics UNIT 1 INTRODUCTION to Biopharmaceutics and Pharmacokinetics Compiled by: Cristopherson P. Mata, RPh, MS Pharm Sources: Towzer and Rowland: Essentials of Pharmacokinetics and Pharmacodynamics, 2 nd edition Katzung, B.G. et al. Basic and Clinical Pharmacology, 13th edition Brenner, G.M. et al. Pharmacology, 4th edition PK & PD action of the drugs (MOA, EFFECT, RESPONSE OF THE BODY ONCE DRUG IS what the katawan does to the drug ADMINISTERED) - g PHARMACOKINETICS ADME O PHARMACODYNAMICS drug-body fate or disposition of the drug → Branch of pharmacology dedicated to determine the → Branch of pharmacology that studies the action of drugs in fate of substances administered living organism. target organs - → “What the& body does to the drug?” ▪ ~ Mechanisms of drug action - ▪ ~Relationship between drug concentration and effect → Absorption, Distribution, Metabolism, and Excretion - Alteration design of (therapeutic, toxic, side effects) INTENDED EFFECT EFFECT OF DRUGS AT HIGHER CONC. Liberation ① - not part of PK - 2 phases disintegration and ② dissolution - not all drugs undergo liberation (IE. IV) Unlike oral Absorption - topical: disappearance of the drug at the site of application - systemic drugs: Gl Distribution &- entry of drug molecules into the different tissues or site of action - Metabolism - the inactivation of the drug to - its inactive components - exception:e produgs (pag nag undergo ng metabolism, naaactivate) Excretion PK & PD BLOOD O CONCENTRATION VS. TIME PHARMACOKINETICS O ▪ Adjustable factors (physicochemical properties of the drug, dosage form, route of administration) ▪ Concentration achieved VS Time (time-course of the body’s handling of a drug) A Katawan ↳ ilang or as na ganito and mg sa effect ⑧ PHARMACODYNAMICS - drug conc. VS response ex. Hypnosis ▪ Drug concentration VS Body’s response to drug exposure (magnitude of drug effect) Drug release Drug in systemic Drug in Pharmacologic/ and absorption circulation tissues Clinical Effect LA - D Metabolism and ME Excretion PK & PD effects ↑ combination of PD and PK Outcome is highly dependent on the pharmacokinetics of the drug E.g. the conc of the drug is below therapeutic window so walang effect. THE EFFECTS YOU DONT WANT Toxic Ph Adequate delivery of the drug to its site of action ensures therapeutic effects - THE EFFECT YOU WANT E NO THERAPEUTIC EFFECT subtherapeutic of amt in ⑳ body the PK & PD Al + excipients Drug properties and formulation ~ ~ (dosage form and route of ~ ~ administration) age & Physiologic factors affecting genetics bioavailability of the drugs. ,Pathologic factors affecting liver Kidney my , ~ (x & prob buccal bioavailability of drugs. ~ oral Sc , , e.g. may renal impairment ~ (IVIMS, si patient, so hindi mo ~ > - (X per day) once we know these ibibigay yung dose na 1 wk , 1 month ~ , ( information, we can ibibigay mo sa walang renal (every 3. mos answer these questions impairment QUANTITATIVE BASIS OF DRUG THERAPY & Possible Adjustments Amount of dose administered (How much?) Gaano Kadami Frequency of administration (How often?) Gaano Kadalas Duration of treatment (For how long?) Gaano Kahaba PHARMACOKINETICS - focused on patient care CLINICAL PHARMACOKINETICS - → Application of PK methods to drug therapy in patient care. nakikita sa hospital setting dahil naiindividualized yung therapeutic regimen → Involves multidisciplinary approach to individually optimized dosing strategies based on: the patient’s diseased state (e.g., renal, hepatic) the patient-specific considerations (e.g., genetics) Application: THERAPEUTIC DRUG MONITORING (TDM) DIRECTLY monitoring plasma drug concentration blood is assayed; KUKUHANAN SI PATIENT NG BLOOD para malaman yung PDC monitoring pharmacodynamic endpoints THESE COULD BE OBJECTIVE OR SUBJECTIVE; eg. if the patient uses phenytoin (anticonvulsant), anong endpoint yung dapat makita: stagmus (above therapeutic window na kasi initial sign of toxicity) → Usually conducted for very potent drugs, such as those another example, lithium (Manic), endpoint is nausea and vomiting so above therapeutic window na yon dahil initial sign of with narrow therapeutic range in order to optimize toxicity na) efficacy and to prevent any adverse toxicity. Phenytoin ① Anticonvulsant stagmus ② Lithium Manic # &f bipolar , depression PK & PD Studies in Drug Development subdivided into 2 phases Phase 0 , 1 , 2 , 3 we do not make use of humans, we use PM animals and other in vitro methods - - - phase 4 ① potential ~ ② para mareport yung mga previously ~ - hindi alam na ADRs para mailagay sa package insert - age gender , , weight large trials. subjects are patients with comorbidities healthy human volunteers hindi para sakanila yung drug dahil wala naman silang sakit so di malalaman yung tests efficacy because we check efficacy patients with the disease that the drug targets  BIOPHARMACEUTICS Is a field of science that examines the interrelationship of the: tablet vs syrup Dosage form Physicochemical Route of drug (drug product) in which properties of the drug administration the drug is given structure on the RATE and EXTENT of systemic drug absorption bioavailability Drug concentration Compare the following using the graph on the left following systemic absorption in blood Lipophilic VS Lipophobic SC VS Oral Oral Solution VS Tablet Time (hr)