Chronopharmacology: optimum administration time.

Hassan A and Haefeli WE analyzed 42 randomized control trials reporting the impact of timing of drug administration on pharmacokinetics, pharmacodynamics, adverse drug reactions and surrogate and clinical endpoints. They identified 33 active ingredients:

• The timing had no impact for 11 substances: nisoldipine, fluoxetine, doxazosin, ranitidine, famotidine, lansoprazole, fluvastatin, isradipine, trandolapril, ciclesonide and diltiazem;

• Morning administration was suggested for amlodipine, perindopril, omeprazole, and pantoprazole;

• Evening administration was favored for theophylline, methylprednisolone, simvastatin, cimetidine, rabeprazole, carboplatin, quinapril, indometacin, isradipine (in hypertensive patients with renal failure) and atorvastatin;

• Bedtime administration was suggested for aspirin (in essential hypertension), valsartan, telmisartan, olmesartan, ramipril and torasemide;

• Twice daily administration (morning & afternoon) was recommended for prednisolone;
• Finally, no recommendation could be given for ketoprofen because of conflicting data.

Authors underlined the following limitations:

• Not all clinical trials studied clinical or surrogate endpoints and adverse reactions;
• Some trials are conducted in healthy volunteers or in too few subjects;
• Duration of clinical trials is often short;
• Dose and indication may change recommendations.

I would also add that we should take into account the timing that would best improve adherence: when is the best time for the patient to take his medication and to prevent missed doses?

Nevertheless, this review should help us improve drug regimens of our patients.

Hassan A, Haefeli WE. Appropriateness of timing of drug administration in electronic prescriptions. Pharm World Sci. 2010;32(2):162-171. Abstract.