一种关于克拉霉素对健康志愿者口腔和鼻腔微生物群影响的药代动力学/药效学方法。

A PK/PD approach on the effects of clarithromycin against oral and nasal microbiota of healthy volunteers.

作者信息

Del Bortolo Ruenis A P, Nobre Franco G C, Baglie S, Lopes Motta R H, Simões R P, Rosalen P L, Franco L M, Moreno R A, Abib E, Groppo F C

机构信息

Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, Brazil.

出版信息

Int J Clin Pharmacol Ther. 2009 Feb;47(2):96-103. doi: 10.5414/cpp47096.

DOI:10.5414/cpp47096

PMID:19203565

Abstract

OBJECTIVE

To assess the pharmacokinetics of clarithromycin (CLR) and its effects on oral and nasal microbiota in healthy volunteers in an open, randomized, two-period crossover design.

METHODS

A single 500 mg oral dose of CLR (Group 1: Merck; Group 2: Klaricid) was administered observing a 1-week interval between doses. Blood samples were collected from pre-dose to 24 h. Plasmatic concentrations of CLR were quantified by the LC-MS-MS method. Saliva and nasal mucosa swabs were obtained previously and after 1.33, 2, 6 and 12 h of drug administration. Pharmacokinetics and PK/PD (t > MIC, %t > MIC and AUC0-24/MIC ratio) parameters were estimated. The microorganism counts were obtained on different culture media.

RESULTS

No statistically significant differences were observed between the two formulations (p > 0.05) regarding the pharmacokinetic parameters. Total microorganisms, staphylococci and streptococci counts did not show statistical differences (p > 0.05) between the two groups during each sampling time. Considering the microorganisms of each group, no statistically significant differences were found after drug administration, but all differed from pre-dose counts (p < 0.05). The observed t > MIC ranged from 14.45 h (+/- 1.69) to 1.19 h (+/- 2.17) considering MICs of 0.25 microg/ml and 2.0 microg/ml, respectively. There was no correlation between any t > MIC, %t > MIC or AUC0-24 and bacterial reduction (between 0- and 12-h periods). However, the profile of reduction of microorganisms in both saliva and nasal samples were compatible with high values of t > MIC verified for both clarithromycin formulations.

CONCLUSION

Both formulations of clarithromycin had similar pharmacokinetics and efficacy.

摘要

目的

采用开放、随机、两周期交叉设计，评估克拉霉素（CLR）在健康志愿者体内的药代动力学及其对口腔和鼻腔微生物群的影响。

方法

单次口服500mg CLR（第1组：默克公司产品；第2组：克拉仙），两次给药间隔1周。给药前至24小时采集血样。采用液相色谱-串联质谱法测定血浆中CLR浓度。给药前以及给药1.33、2、6和12小时后采集唾液和鼻黏膜拭子。估算药代动力学和PK/PD（t＞MIC、%t＞MIC和AUC0-24/MIC比值）参数。在不同培养基上进行微生物计数。

结果

两种制剂的药代动力学参数无统计学显著差异（p＞0.05）。两组在各采样时间的总微生物、葡萄球菌和链球菌计数无统计学差异（p＞0.05）。就每组微生物而言，给药后未发现统计学显著差异，但均与给药前计数不同（p＜0.05）。分别考虑0.25μg/ml和2.0μg/ml的MIC时，观察到的t＞MIC范围为14.45小时（±1.69）至1.19小时（±2.17）。任何t＞MIC、%t＞MIC或AUC0-24与细菌减少量（0至12小时期间）之间均无相关性。然而，唾液和鼻腔样本中微生物减少的情况与两种克拉霉素制剂验证的高t＞MIC值相符。