TEMPORAL VARIATION IN DRUG ABSORPTION

The main aim of chronokinetics studies is to control the time of administration which among others, can not only be responsible for verification of drug kinetics but also may explain chronopharmacological effects observed with certain drugs.

Passive diffusion is by far the most important process in the mechanism of drug absorption. Absorption after oral drug dosing can be influenced by the physio-chemical properties of the drug, the area and the structure of the bio-membrane, gastric emptying, pH and motility and gastro-intestinal blood flow. In the light of circadian variations, there are several reports on temporal variations of drug absorption.

Most of the drugs seem to have higher rate or extent of bioavailability when they are administered in the morning than when they are taken in the evening.
For example, with cardiovascular drugs such as nifedipine, oral nitrates and proponolol, a plasma peak concentration are twice as high and times to peak concentrations are shorter after morning dosing as after evening administration. The underlying mechanisms is their chronopharmacokinetic pattern and involves a faster gastric emptying time and greater gastrointestinal perfusion in the morning.

Atenolol, in contrast to propronolol, is not absorbed more rapidly after morning administration compared with evening administration . This confirms that the absorption rate of lipophillic drugs after morning dosing is faster than the same characteristic of hydrophilic drug.

The influence of chronokinetic of the route of administration must also be considered. For example, there are studies showing that chronopharmacokinetic variation is not found when drug is administered rectally.

In children, the skin penetration of an eutectic mixture of lidocaine and priliocaine was reported to depend on the time of administration, with a higher rate of penetration occurring in the evening.

Circadian dose administration time – dependency in the forearm skin penetration of hydrophilic methylnicotinate and lipophillic hexylnicotinate was demonstrated . Circadian variations have also been reported in the ocular absorption of topically applied timolol.