Drug Absorption
There are several different routes of drug administration: intravenous, oral, buccal, sublingual, rectal, subcutaneous, transdermal, topical, inhaled and intramuscular.
Orally administered drugs enter the intestine before entering circulation. Buccal and sublingual administration involves the drug dissolving in the mouth so it directly enters circulation.
Skin in different areas of the body has different levels of fat and muscle beneath it which needs to be considered when dosing and administering.
Bioavailability is the fraction of drug absorbed into systemic circulation. Bioavailability differs depending on route of administration.
Drugs given by IV injection have 100% absorption and 100% bioavailability.
Drugs given by intramuscular or subcutaneous injection have 100% absorption but <100% bioavailability.
Orally administered drugs have <100% absorption and 0 to 60% bioavailability.
Barriers to absorption depending on route of administration, drug factors and patient factors all affect drug absorption.
Barriers to absorption by different routes: no barriers to IV absorption, the gastrointestinal mucosa is a barrier to absorption by oral administration, and the skin epithelium and subcutaneous tissues are barriers to absorption by topical administration.
Drug factors which affect rate and extent of absorption include molecular size, lipid solubility, ionisation at physiological pH, chemical form and pharmaceutical nature of the drug.
Patient factors which affect rate and extent of absorption include surface area of absorptive surface, blood flow to the site of absorption and (oral drugs only) stomach emptying and intestinal transit.
Factors which affect membrane penetration rate are surface area, concentration gradient, lipid solubility, molecular weight and membrane thickness.
Drugs may enter cells by passive diffusion, carrier-mediated transport, pore-mediated transport or pinocytosis.
Solid dosage form drugs are taken orally. Disintegration of the dosage form must then occur (unless drug in capsule form) after which point the drug particles dissolve. Only soluble material may then be absorbed. Dissolved drug particles are absorbed across the membrane.
Formulation of drug affects its pharmacokinetic profile. Drugs in liquid/solution form undergo rapid absorption in as little as 10 minutes. Immediate-release tablets break down in around half an hour and absorption takes 1 hour therefore effects are felt in around 1.5 hours. Modified release tablets break down more slowly after a longer period of time so that effects of the drug aren’t as immediate but occur for longer.
In industry, extensive testing occurs in cell culture and preclinical animal studies before human testing can occur. Many of these tests are to either predict or measure pharmacokinetic properties .
An investigational new drug document is written about the potential of a new substance, covering all disciplinary areas. Reports included in the IND cover preclinical studies, chemistry, manufacturing and controls (CMC), protocols for clinical studies and an investigational plan for clinical development which covers at least the first year.
Areas included in the IND related to pharmacology include details on pre-clinical animal studies and pharmacokinetics supporting the clinical programme, pharmacokinetics underpinning the toxicity assessment, justification of clinical testing in humans, in vitro models which predict specific aspects of pharmacokinetics, and in silico models predicting overall pharmacokinetics in a diverse range of patients.
Justification of clinical testing in humans involves extrapolation from animal data to understand how the ADME and PK data translates into humans
IND for phase I trials has 5 or less pages on pharmacology and drug distribution and 10 to 15 pages on toxicology, and identification and qualifications of individuals who have decided human trials are safe to start.
There are several different routes of drug administration: intravenous, oral, buccal, sublingual, rectal, subcutaneous, transdermal, topical, inhaled and intramuscular.
Orally administered drugs enter the intestine before entering circulation. Buccal and sublingual administration involves the drug dissolving in the mouth so it directly enters circulation.
Skin in different areas of the body has different levels of fat and muscle beneath it which needs to be considered when dosing and administering.
Bioavailability is the fraction of drug absorbed into systemic circulation. Bioavailability differs depending on route of administration.
Drugs given by IV injection have 100% absorption and 100% bioavailability.
Drugs given by intramuscular or subcutaneous injection have 100% absorption but <100% bioavailability.
Orally administered drugs have <100% absorption and 0 to 60% bioavailability.
Barriers to absorption depending on route of administration, drug factors and patient factors all affect drug absorption.
Barriers to absorption by different routes: no barriers to IV absorption, the gastrointestinal mucosa is a barrier to absorption by oral administration, and the skin epithelium and subcutaneous tissues are barriers to absorption by topical administration.
Drug factors which affect rate and extent of absorption include molecular size, lipid solubility, ionisation at physiological pH, chemical form and pharmaceutical nature of the drug.
Patient factors which affect rate and extent of absorption include surface area of absorptive surface, blood flow to the site of absorption and (oral drugs only) stomach emptying and intestinal transit.
Factors which affect membrane penetration rate are surface area, concentration gradient, lipid solubility, molecular weight and membrane thickness.
Drugs may enter cells by passive diffusion, carrier-mediated transport, pore-mediated transport or pinocytosis.
Solid dosage form drugs are taken orally. Disintegration of the dosage form must then occur (unless drug in capsule form) after which point the drug particles dissolve. Only soluble material may then be absorbed. Dissolved drug particles are absorbed across the membrane.
Formulation of drug affects its pharmacokinetic profile. Drugs in liquid/solution form undergo rapid absorption in as little as 10 minutes. Immediate-release tablets break down in around half an hour and absorption takes 1 hour therefore effects are felt in around 1.5 hours. Modified release tablets break down more slowly after a longer period of time so that effects of the drug aren’t as immediate but occur for longer.
In industry, extensive testing occurs in cell culture and preclinical animal studies before human testing can occur. Many of these tests are to either predict or measure pharmacokinetic properties .
An investigational new drug document is written about the potential of a new substance, covering all disciplinary areas. Reports included in the IND cover preclinical studies, chemistry, manufacturing and controls (CMC), protocols for clinical studies and an investigational plan for clinical development which covers at least the first year.
Areas included in the IND related to pharmacology include details on pre-clinical animal studies and pharmacokinetics supporting the clinical programme, pharmacokinetics underpinning the toxicity assessment, justification of clinical testing in humans, in vitro models which predict specific aspects of pharmacokinetics, and in silico models predicting overall pharmacokinetics in a diverse range of patients.
Justification of clinical testing in humans involves extrapolation from animal data to understand how the ADME and PK data translates into humans
IND for phase I trials has 5 or less pages on pharmacology and drug distribution and 10 to 15 pages on toxicology, and identification and qualifications of individuals who have decided human trials are safe to start.
