Trimethoprim在家兔體內的動態   全文下載

Absorption and Disposition Kinetics of Trimethoprim following Intramuscular Injection in Rabbits

本文報告以九隻紐西蘭雄性白兔（2.67 ± 0.16 kg）探討抗菌藥Trimethoprim （TMP） 經靜脈及肌肉注射後之體內動態，作為開發TMP肌肉注射劑型之基礎資訊。以TMP乳酸鹽溶液（TMPL） 15.3 mg ／ kg 劑量靜脈注射後，其血中TMP之經時變化可用二室體模式加以歸納（ C=Ae-λ1t+Be-λ2t。其藥物動力學速率常數及動力學參數分別為λ1 : 6.72 ± 2.37 h-1，λ2 : 0.898 ± 0.149 h-1, k10 : 1.81 ± 0.24 h-1, k12 : 2.48 ± 1.25 h-l, k21 : 3.34 ± 1.31 h-1, V1 : 1.87 ± 0.21 l, V2: 1.39 ± 0.91, Cl : 1. 25 ± 0.12 l／h／kg。肌肉注射TMPL及TMP glycofurol溶液（TMPG）後， TMP皆完全吸收（F=1.0）。然而TMPL注射後TMP之吸收遠比注射TMPG快速。其平均吸收時間各為TMPL : 0 .4 ± 0.1h，而TMPG : 1.0 ± 0.1h。注射TMPL於肌肉後之Cmax為8.91 ± 1.48 mg／l 也比注射TMPG後之Cmax 5.97 ± 0.88 mg／l 為高。TMP在家兔血球內之分佈分率各為0.388 ± 0.015（靜注）和0.279 ± 0.019（肌注）。"

The absorption and disposition kinetics of an antimicrobial agent, trimethoprim (TMP) were investigated using New Zealand white male rabbits. The blood and plasma concentration- time curves obtained subsequent to the intravenous administration of trimethoprim lactate solution (TMP 15.3 mg/kg body weight) were fitted to a two-compartment body model (C=Ae-λ1t + Be-λ2t). The rate constants of TMP based on the blood data wereλ1: 6.72 ± 2.37 h-1 (mean ± SD); λ2 0.898 ± 0.149 h-1; k10: 1.81 ± 0.24 h-1; k12: 2.48 ± 1.25 h-1; k21: 3.34 ± 1.31 h-1 and the volumes of distribution were V1: 1.87 ± 0.211 and V2: 1.39 ± 0.91 (2.67 ± 0.16 kg body weight). The body clearance of TMP was 1.25 ± 0.12 l/h/kg. The availability of TMP in lactate (TMPL) and in glycofurol (TMPG) solutions administered to the vastus lateralis muscle was equivalent to that of the intravenous administration at the same dosage. However, the mean absorption time (MAT) of TMP from muscle was significantly shorter with TMPL solution (0.4 ± 0.1 h) than with TMPG solution ( 1.0 ± 0.1 h). The mean Cmax obtained with TMPL (8.91 ± 1.48 mg/l) was higher than that obtained with TMPG (5.97 ± 0.88 mg/l). The fraction of TMP in the rabbit blood cells averaged 0.388 ± 0.015 (i.v.) and 0.279 ± 0.019 (i.m.). 本文報告以九隻紐西蘭雄性白兔（2.67 ± 0.16 kg）探討抗菌藥Trimethoprim （TMP） 經靜脈及肌肉注射後之體內動態，作為開發TMP肌肉注射劑型之基礎資訊。以TMP乳酸鹽溶液（TMPL） 15.3 mg ／ kg 劑量靜脈注射後，其血中TMP之經時變化可用二室體模式加以歸納（ C=Ae-λ1t+Be-λ2t。其藥物動力學速率常數及動力學參數分別為λ1 : 6.72 ± 2.37 h-1，λ2 : 0.898 ± 0.149 h-1, k10 : 1.81 ± 0.24 h-1, k12 : 2.48 ± 1.25 h-l, k21 : 3.34 ± 1.31 h-1, V1 : 1.87 ± 0.21 l, V2: 1.39 ± 0.91, Cl : 1. 25 ± 0.12 l／h／kg。肌肉注射TMPL及TMP glycofurol溶液（TMPG）後， TMP皆完全吸收（F=1.0）。然而TMPL注射後TMP之吸收遠比注射TMPG快速。其平均吸收時間各為TMPL : 0 .4 ± 0.1h，而TMPG : 1.0 ± 0.1h。注射TMPL於肌肉後之Cmax為8.91 ± 1.48 mg／l 也比注射TMPG後之Cmax 5.97 ± 0.88 mg／l 為高。TMP在家兔血球內之分佈分率各為0.388 ± 0.015（靜注）和0.279 ± 0.019（肌注）。