Although our website is oriented toward child and adolescent psychiatry, this review of drug metabolism will not be limited to pediatric topics. The subject matter is very important for all doctors and is extensively tested on PRITEs and Boards. Child-specific considerations will be addressed in a dedicated section below.
Absorption is the process of getting the drug into the bloodstream.
Bioavailability, a subcategory of absorption, is fraction of medication that reaches systemic ciculation. Bioavailablity of IV medications is by definition 100%.
Absorption of PO medications takes place in the GI tract, maily in the small intestine, and thus affected by a number of factors:
- GI tract conditions (acidity, presence of food, chronic inflammation, gut flora, acute diarrhea or emesis, gastric emptying rate)
- Physcial properties of the drug (pKa, solubility, hydrophobicity)
- Presence of specific drugs and foods that interact with the medication
- First-pass metabolism (may vary significantly from person to person)
The half-life of a drug is the time required for the concentration of a drug to decrease by 50%.
A steady-state concentration is an equilibrium state between the amount of drug injested and eliminatied. A steady-state is reached after a drug had been taken regularly for the duration of 4-5 half-lives. This is often confused with 4-5 doses, since most drugs that we check levels on are dosed at intervals close to their half-lives:
- Depakote t1/2 = 12 hrs, and it is often given BID. Thus, Depakote will reach a steady state in 2-2.5 days (4-5 BID doses);
- Lithium t1/2 = 12-27 hrs, usually given BID or qHS; a steady-state is reached in 2-5 days depending on age and renal function, which can mean up to 10 doses if taken BID by an elderly patient);
- For Prozac, which can have a half-life of 5-6 days in those taking it chronically, it can take 3 weeks to reach a steady-state after a change in a dose.
Pharmacokinetics in children and adolescents
- Capacity to metabolize and eliminate a drug is low at birth, but rises rapidly to adult levels by 2 years of age.
- At puberty metabolic and eliminatory capacity may actually exceed those of an adult, requiring higher doses in adolescents.
- Children also have higher proprtion of body water and less adipose tissue, affecting distribution of particular drugs.
- Half-life of a drug, not the number of doses, determine how soon the steady-state concentration is achieved.
- Same principle applies to to elimination of the drug, i.e. the half-life, not the number of missed doses determine how much of drug remains in the body.