Bagley D M, Lin Y J
Research and Development Division, Colgate-Palmolive Company, Piscataway, NJ 08855-1343, USA.
Am J Dent. 2000 Jun;13(3):148-52.
To demonstrate through clinical pharmacokinetic studies that triclosan does not accumulate in blood or plasma in human subjects who regularly use triclosan-containing dentifrice.
Three clinical pharmacokinetic studies were conducted to assess the blood or plasma levels of triclosan following toothbrushing with dentifrice formulations containing triclosan. In Study 1, both a single-dose and a multiple-dose phase were conducted. In the single-dose phase, subjects brushed one time with 1.25 g dentifrice containing 0.3% triclosan (3.75 mg triclosan dose) and ingested all of the dentifrice. Blood samples were collected at multiple time points from pre-dose to 72 hrs post-dose and analyzed for total triclosan levels. In the multiple-dose phase, these same subjects brushed three times daily as in the single-dose phase. This pattern was followed for 12 consecutive days. Blood samples were taken for triclosan analysis at multiple time points up to 48 hrs after the first dose of day 12. Study 2 was a parallel, open-labeled clinical study to compare triclosan blood levels from twice daily brushing with 1 gm of dentifrice containing 0.2% triclosan to twice daily ingestion of 20 ml of a 0.01% triclosan aqueous solution over a period of 21 days. Blood samples were taken for triclosan analysis at baseline and at 4 hrs after the morning dose on days 7, 14, and 21. Study 3 was a parallel, double-blind, 12-wk brushing study with dentifrice containing 0.2% triclosan or a matching placebo. Blood samples were taken for triclosan analysis at baseline and at 3 and 12 wks at 4 hrs after the morning dose.
In the single-dose study, Triclosan was absorbed into the systemic circulation with a T(1/2) of the terminal plasma concentration ranging between 6-63 hrs. The mean AUC(0-inf) after a single dose was found to be 2,809 ng x hr/ml. After 12 days of three times daily toothbrushing and ingestion of the dental slurry, the mean triclosan plasma concentration was 352 ng/ml in the steady state period, and the mean AUC in a 24-hr period (AUC24) was found to be 8,460 ng x hr/ml. This AUC24 was normalized for the number of brushings for comparison to the AUC(0-inf) after a single brushing. There was no significant (P = 0.93) difference between these AUC values suggesting a complete elimination of daily triclosan dose and no increase in the triclosan level during repeated brushing/ingestion. In the two other dentifrice studies, the triclosan blood concentration appeared to reach a steady state level by day 7 and was maintained at the steady state level (14 to 21 ng/ml) for up to 12 wks. These results support the conclusion that the elimination of a daily triclosan dose is complete and no accumulation of triclosan was observed even after three times daily toothbrushing with 1.25 g dentifrice containing 0.3% triclosan and full ingestion of the dentifrice.
通过临床药代动力学研究证明,对于经常使用含三氯生牙膏的人体受试者,三氯生不会在血液或血浆中蓄积。
进行了三项临床药代动力学研究,以评估使用含三氯生牙膏刷牙后三氯生的血液或血浆水平。在研究1中,进行了单剂量和多剂量阶段。在单剂量阶段,受试者用1.25克含0.3%三氯生的牙膏(3.75毫克三氯生剂量)刷牙一次,并将所有牙膏咽下。在给药前至给药后72小时的多个时间点采集血样,分析总三氯生水平。在多剂量阶段,这些受试者与单剂量阶段一样,每天刷牙三次。这种模式持续12天。在第12天首次给药后长达48小时的多个时间点采集血样进行三氯生分析。研究2是一项平行、开放标签的临床研究,比较每天两次使用1克含0.2%三氯生的牙膏刷牙与每天两次摄入20毫升0.01%三氯生水溶液在21天内的三氯生血液水平。在基线以及第7、14和21天早晨给药后4小时采集血样进行三氯生分析。研究3是一项平行、双盲、为期12周的刷牙研究,使用含0.2%三氯生的牙膏或匹配的安慰剂。在基线以及第3和12周早晨给药后4小时采集血样进行三氯生分析。
在单剂量研究中,三氯生被吸收进入体循环,终末血浆浓度的T(1/2)在6 - 63小时之间。单次给药后的平均AUC(0-inf)为2,809纳克·小时/毫升。在每天刷牙三次并咽下牙膏浆液12天后,稳态期的平均三氯生血浆浓度为352纳克/毫升,24小时期间的平均AUC(AUC24)为8,460纳克·小时/毫升。该AUC24针对刷牙次数进行了标准化,以便与单次刷牙后的AUC(0-inf)进行比较。这些AUC值之间无显著差异(P = 0.93),表明每日三氯生剂量被完全清除,且在重复刷牙/咽下过程中三氯生水平未升高。在另外两项牙膏研究中,三氯生血液浓度在第7天似乎达到稳态水平,并在长达12周的时间内维持在稳态水平(14至21纳克/毫升)。这些结果支持以下结论:每日三氯生剂量被完全清除,即使每天三次使用1.25克含0.3%三氯生的牙膏并完全咽下牙膏,也未观察到三氯生蓄积。