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
Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, Brazil.
Int J Clin Pharmacol Ther. 2009 Feb;47(2):96-103. doi: 10.5414/cpp47096.
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.
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.
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.
Both formulations of clarithromycin had similar pharmacokinetics and efficacy.
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。
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。
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。
两种克拉霉素制剂具有相似的药代动力学和疗效。
