Biopharmaceutics and pharmacokinetic by: Anjam Hama A. M. Sc Biopharmaceutics and pharmacokinetic by: Anjam Hama A. M.Sc. Pharmaceutics HMU/ College of pharmacy ahabdalla@pha.hmu.edu.iq 15/02/2018

Lecture outline What is Biopharmaceutics? Factors involve in Biopharmaceutics Definition of Pharmacokinetic (PK) Definition of pharmacodynamics (PD) Aim of PK and PD Why we study pharmacokinetics? 15/02/2018

What is biopharmaceutic? Biopharmaceutics: the study of how the physicochemical properties of drugs, dosage forms and routes of administration affect the rate and extent of the drug absorption. Biopharmaceutics: consider the properties of the drug and the dosage form in physiological environment, the drugs intended therapeutic use and the route of administration. What are those factors have impact on bio pharmaceutics? 15/02/2018

Factors involve in Biopharmaceutics The stability of the API within the drug products The release of API within the drug products The rate of dissolution/ release of API with the drug products The systemic absorption of the API 15/02/2018

The study of biopharmaceutic is based on scientific principles and experimental methodology. Study in biopharmaceutics use both invitro and in-vivo method. In-vivo methods: are more complex studies involving human subjects or laboratory animals. Example ? 15/02/2018

Invitro methods: Examples? They are procedures employing test apparatus and equipments without involving human or experimental animals. Examples? 15/02/2018

Biopharmaceutics pharmacokinetics pharmacodynamic Kinetics of drug absorption, distribution, elimination (M and E) pharmacodynamic Concentration of the drug at the site of action & pharmacological response. 15/02/2018

PK and PD PK is the study of what the body does to a drug PD is the study of what a drug does to the body ADME: is an acronym in pharmacokinetics and pharmacology for a absorption, distribution, metabolism, and excretion, and describes the disposition of pharmaceutical compound within anorganism. 15/02/2018

pharmacokinetic Pharmacokinetics: is the science of kinetic of drug absorption distribution and elimination (metabolism and excretion). The study of pharmacokinetic involve both experimental and theoretical approach. The experimental aspects: involve the development of biological sampling techniques, analytical methods for the measurement of drugs and metabolites and procedure that facilitate data collection and manipulation. 15/02/2018

The theoretical aspects of pharmacokinetics involves the developments of pharmacokinetics models that predict drug disposition after drug administration 15/02/2018

Absorption: is the process of a substance entering the body. Distribution: is the dispersion of substances throughout the fluids and tissues of the body. Metabolism: is the irreversible transformation of parent compounds in to daughter metabolites. Excretion: Is the elimination of the substances from the body 15/02/2018

Absorption Must be able to get medications into the patient’s body. Drug characteristics that affect absorption: Molecular weight, ionization, solubility, & formulation Factors affecting drug absorption related to patients: Route of administration, gastric pH, contents of GI tract 15/02/2018

Absorption in the Pediatric Patient Gastrointestinal pH changes Gastric emptying Gastric enzymes Bile acids & biliary function Gastrointestinal flora Formula/food interaction 15/02/2018

Time to Peak Concentration 15/02/2018

Distribution Membrane permeability cross membranes to site of action Plasma protein binding bound drugs do not cross membranes malnutrition = albumin =  free drug Lipophilicity of drug lipophilic drugs accumulate in adipose tissue Volume of distribution 15/02/2018

Pediatric Distribution Body Composition  total body water & extracellular fluid  adipose tissue & skeletal muscle  neonates and young infants require larger loading doses of phenobarbital to attain plasma concentrations similar to those in adults. Protein Binding albumin, bilirubin, 1-acid glycoprotein reach adult level after one year Tissue Binding compositional changes 15/02/2018

Metabolism Drugs and toxins are seen as foreign to patients bodies Drugs can undergo metabolism in the lungs, blood, and liver Body works to convert drugs to less active forms and increase water solubility to enhance elimination 15/02/2018

Metabolism Liver - primary route of drug metabolism Liver may be used to convert pro-drugs (inactive) to an active state Types of reactions Phase I (Cytochrome P450 system) Phase II 15/02/2018

Elimination Pulmonary = expired in the air Bile = excreted in feces enterohepatic circulation Renal glomerular filtration tubular secretion 15/02/2018

Pediatric Elimination Glomerular filtration matures in relation to age, adult values reached by 3 yrs of age Neonate = decreased renal blood flow, glomerular filtration, & tubular function yields prolonged elimination of medications Aminoglycosides, cephalosporin's, penicillin's = longer dosing interval 15/02/2018

Effects of age on pharmacokinetic parameters affecting drug disposition igure 46.1 Effects of age on pharmacokinetic parameters affecting drug disposition. The shadows represent the relative rate of cytochrome P450 (CYP) activity. aUGT (uridine diphosphate glucuronosyltransferase) activity is initially decreased in the infant and reaches adult levels by 4 years of age. bUGT activity is decreased in the elderly only in some drugs but remains approximately the same with others. (From Morselli PL, Pippenger CE. Drug disposition during development: an overview. Am Assoc Clin Chem 1979;1-8, with permission.) 15/02/2018

pharmacodynemics Pharmacodynemics: refers to the relationship between the drug concentration at the site of action (receptor) and pharmacological response, including ( biochemical) and (physiologic) effects that influence the interaction of drug with the receptor. The interaction between the receptor and drug molecules coused the initiating of sequence of molecular events resulting in pharmacological or toxic eresponse. 15/02/2018

Why Study Pharmacokinetics (PK) and Pharmacodynamics (PD)? Individualize patient drug therapy Monitor medications with a narrow therapeutic index Decrease the risk of adverse effects while maximizing pharmacologic response of medications Evaluate PK/PD as a diagnostic tool for underlying disease states 15/02/2018

Summery of Drug after administration 15/02/2018

References Applied biopharmaceutics and pharmacokinetics seven addition by leon shargel 15/02/2018