Faculty of Pharmacy, The University of Sydney, NSW, Australia.
J Pharm Pharmacol. 2011 Sep;63(9):1161-8. doi: 10.1111/j.2042-7158.2011.01326.x. Epub 2011 Jul 6.
To investigate the utility of metrics of CYP1A2 activity using caffeine as a probe, and saliva and plasma sampling with or without a 24-h caffeine abstinence.
This was a cross-over pharmacokinetic study in 30 healthy male subjects who received a single oral 100mg caffeine dose after 24-h caffeine abstinence or after maintaining their regular caffeine intake (no caffeine abstinence). Serial blood and saliva samples were collected simultaneously over 24h. Caffeine and paraxanthine concentrations were measured using a validated HPLC assay.
There was a strong correlation between the paraxanthine/caffeine AUC(0-24) ratio (reference metric) and the paraxanthine/caffeine concentration (C(t) ) ratio at 4h (C(4) ) in both saliva and plasma (r≥0.75). The paraxanthine/caffeine AUC(0-24) ratio in plasma and saliva did not differ between the 24-h caffeine abstinence and the no abstinence period (P>0.05). The optimal paraxanthine/caffeine C(t) that correlated with the plasma paraxanthine/caffeine AUC(0-24) ratio in the 24-h abstinence period was 2 and 4h (r=0.88) in plasma, and 4 and 6h in saliva (r=0.70), while it was the saliva 4h time-point in the no abstinence period (r=0.78).
The saliva paraxanthine/caffeine concentration ratio at 4h was a suitable metric to assess CYP1A2 activity after oral administration of caffeine without the need for 24-h caffeine abstinence.
研究以咖啡因作为探针的 CYP1A2 活性指标的效用，并探讨是否需要 24 小时禁饮咖啡因来采集唾液和血浆样本。
这是一项在 30 名健康男性受试者中进行的交叉药代动力学研究，这些受试者在 24 小时禁饮咖啡因或保持常规咖啡因摄入（不禁饮咖啡因）后，单次口服 100mg 咖啡因。在 24 小时内，同时采集连续的血液和唾液样本。使用验证后的 HPLC 测定法测定咖啡因和 1,7-二甲基黄嘌呤（paraxanthine）的浓度。
在唾液和血浆中，4 小时时的 paraxanthine/咖啡因 AUC(0-24)比值（参考指标）与 paraxanthine/咖啡因浓度（C(t)）比值之间存在很强的相关性（r≥0.75）。在 24 小时禁饮咖啡因和不禁饮咖啡因期间，血浆和唾液中的 paraxanthine/咖啡因 AUC(0-24)比值无差异（P＞0.05）。与血浆中 paraxanthine/咖啡因 AUC(0-24)比值相关性最佳的 paraxanthine/咖啡因 C(t)值在禁饮咖啡因 24 小时期间分别为 2 小时和 4 小时（r=0.88），在不禁饮咖啡因期间分别为 4 小时和 6 小时（r=0.70），而在唾液中为 4 小时时（r=0.78）。
在无需 24 小时禁饮咖啡因的情况下，口服咖啡因后，4 小时唾液中 paraxanthine/咖啡因浓度比值是评估 CYP1A2 活性的合适指标。
