TEMPORAL VARIATION IN DRUG ABSORPTION

Elucidating my topic with the examples of various drugs it follows as;
Changes in the pharmacokinetics of indomethacin is dependent on time dosing.
A circadian rhythm of both peak height and time-to-peak was detected.

Changes in the plasma bioavailability of theophylline, dependent on dosing time which are mainly due to the difference in absorption via the digestive tract rather than from circadian rhythmic variations in the renal clearance of theophylline. Large chronokinetic changes occurred when sustained release theophylline preparations were administered via oral route, especially in children, while only minor changes were observed when theophylline was injected intravenously at constant rate.

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Solubility of the drug appears to play an important role in the circadian variations in drug absorption as in case of low water solubility such as indomethacin, furosemide and phenylbutazone, hydrochlorthiazide and paracetamol.

The absorption T½ of the benzodiazepine lorazepam was three times longer with evening rather than morning dosing

It is important to note that meal timing and food intake can neither create circadian rhythms in biological functions nor explain chronokinetic phenomenon but may influence kinetic parameters of some drugs at certain dosing times ( eg. Advance or delay Tmax and / or increase or decrease Cmax, perhaps reflecting day / night differences in gastric emptying. Thus day transit time has no or only minor effects on those changes in day kinetics which are dependent on dosing time.

Endogenous circadian rhythms such are those in gastrointestinal pH, intestinal motility, digestive secretions and intestinal blood flow, among others are the factors which one should take into account to explain the mechanism of chronokinetics drug absorption.