Borin M T, Hughes G S, Patel R K, Royer M E, Cathcart K S
Clinical Pharmacokinetics Unit, Upjohn Company, Kalamazoo, Michigan 49007.
J Clin Pharmacol. 1991 Dec;31(12):1137-45. doi: 10.1002/j.1552-4604.1991.tb03686.x.
Cefpodoxime proxetil, a third generation, broad-spectrum, oral cephalosporin, was administered in single doses of 100, 200, 400, 600, and 800 mg (dose expressed as cefpodoxime equivalents) and multiple doses of 100, 200, and 400 mg twice daily to healthy volunteers. The pharmacokinetics of the active metabolite, cefpodoxime, and tolerance of cefpodoxime proxetil were determined. Results from the single-dose study indicate that cefpodoxime exhibits nonlinear pharmacokinetics over the dose range of 100 to 800 mg. This nonlinearity is primarily due to differences in dose-normalized AUC and Cmax, urinary recovery, and half-life between one or more of the higher-dose treatment groups and the 100-mg dosing group. After multiple-dose (twice daily) administration for 15 days, steady state is achieved on the second day of dosing, and there is no drug accumulation. Cefpodoxime pharmacokinetics are linear with dose over the clinically relevant dosing range of 100 to 400 mg. Microbiologic and HPLC plasma assay results are highly correlated, with close agreement between HPLC- and microbiologic-determined pharmacokinetic parameter estimates. Cefpodoxime proxetil was well tolerated in both studies. The most frequent medical events were related to gastrointestinal problems and consisted of transient loose stools in three subjects in the single-dose study and antibiotic-associated diarrhea in one subject in the multiple-dose study.
头孢泊肟酯是一种第三代广谱口服头孢菌素，以100、200、400、600和800毫克单剂量（剂量以头孢泊肟等效量表示）以及100、200和400毫克每日两次的多剂量给予健康志愿者。测定了活性代谢物头孢泊肟的药代动力学以及头孢泊肟酯的耐受性。单剂量研究结果表明，在100至800毫克的剂量范围内，头孢泊肟呈现非线性药代动力学。这种非线性主要是由于一个或多个高剂量治疗组与100毫克给药组之间在剂量标准化的AUC和Cmax、尿回收率以及半衰期方面存在差异。多次给药（每日两次）15天后，在给药第二天达到稳态，且无药物蓄积。在100至400毫克的临床相关给药范围内，头孢泊肟的药代动力学与剂量呈线性关系。微生物学和HPLC血浆测定结果高度相关，HPLC和微生物学测定的药代动力学参数估计值之间一致性良好。在两项研究中，头孢泊肟酯的耐受性均良好。最常见的医学事件与胃肠道问题有关，单剂量研究中有3名受试者出现短暂性腹泻，多剂量研究中有1名受试者出现抗生素相关性腹泻。
