Can a drug follow both zero order and first order kinetics?

 

Can a drug follow both zero order and first order kinetics?

·         Any exogenous substance including drugs when administered by any route to the human body undergoes metabolism and elimination.

·         Lipid soluble drugs must first undergo metabolism, get converted into water soluble compounds and are then eliminated.

·         Water soluble drugs  get directly eliminated but sometimes, a part of them also undergo metabolism.

·         The process of metabolism and elimination are carried out by enzymes and transporters.

·         Most enzymes and transporters  in the body obey saturation kinetics.

·         So theoretically, all drugs will show first order kinetics at low concentration in plasma and zero order kinetics at high concentration in plasma.

·         However, in clinical pharmacology, we are concerned only about the therapeutic range because the dose and dose interval are planned to keep the drug concentration in the therapeutic range.

·         So, drugs for which the enzymes and transporters are yet not saturated in therapeutic range are said to obey first order kinetics. And drugs for which the enzymes are saturated in therapeutic range are said to obey zero order kinetics.

BIO-EQUIVALENCE

 

BIO-EQUIVALENCE

AUC of the plasma concentration time curves of same drug X, but of different oral formulations A, B and C, are almost same.

So the extent of absorption of the three formulations are same.

However, they are not bio-equivalent.

Reason- The rate of absorption is not same.

For bio-equivalence, both rate and extent of absorption should not be significantly different.

AUC for A and B are similar with respect to both the rate and extent of absorption. AUCs are similar in shape and size. Therefore, formulations A and B are bio-equivalent.

Bioavailability

 

Bioavailability

·         Drugs are absorbed from the site of administration into the systemic circulation.

·         In simple words, the fraction of drug that reaches systemic circulation in unchanged form, from the site of administration is the bioavailability. It not only indicates the rate of absorption but also the extent of absorption.

·         In intravenous route, all of the drug directly enters into systemic circulation. Therefore, the bioavailability is 100%

·         Example-  1000 mg of Drug A is given by oral route. Out of 1000 mg, 800 mg is absorbed from the gut. 200 mg undergoes Hepatic First pass metabolism. So the amount of drug that reaches systemic circulation is 800-200= 600 mg. So bioavailability is (600/1000)x 100= 60 %.

·         In pharmacokinetic, bioavailability of an orally administered drug is determined using the plasma-concentration time curve (see the graph below)