Assessment of the time course of drugs with inhibitory effects on hepatic metabolic activity using successive salivary caffeine tests.
In clinical practice is very important to know the time course of the inhibitory effects of drugs to avoid side effects when several agents are taken concomitantly. We attempted to validate the effectiveness of successive salivary caffeine tests establishing the time for cimetidine to inhibit hepatic metabolism. The time of cimetidine's inhibitory effect as reported in other studies was chosen as the reference. In this open-label, prospective longitudinal, 16-day study, five healthy volunteers were treated with cimetidine 1 g/day for 5 days. After the intake of caffeine 300 mg, salivary caffeine tests were carried out on days -1 (control value), 1, 4, 8, 12, and 16. The mean systemic caffeine clearance was decreased after 24 hours of cimetidine. The drug's maximum inhibitory effect was reached after 5 days of administration, returning to previous values progressively 1-7 days after discontinuing cimetidine. No change occurred in the apparent volume of distribution. The time course of cimetidine's inhibitory effect was similar to that described with other methodologies. Although this was a pilot trial and the results have to be confirmed, it seems that successive salivary caffeine measurements could be a safe, reliable, noninvasive test for exploring the time course of the inhibitory effects of drugs on hepatic metabolism.
Soto
J
J
Clinical Pharmacology Unit, Santa Cruz Hospital, Liencres-Cantabria, Spain.
Alsar
M J
MJ
Sacristan
J A
JA
D000328:Adult; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002110:Caffeine / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D002927:Cimetidine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D008657:Metabolic Clearance Rate; D010865:Pilot Projects; D011446:Prospective Studies; D012463:Saliva / Q000737:chemistry* / Q000378:metabolism
D000897:Anti-Ulcer Agents; D000697:Central Nervous System Stimulants; D002110:Caffeine; D002927:Cimetidine