The clinical pharmacokinetics of ribavirin after a single oral dose of 600 mg ribavirin tablets in healthy Chinese volunteers was studied. A rapid and simple high performance liquid chromatography （HPLC） method was ...The clinical pharmacokinetics of ribavirin after a single oral dose of 600 mg ribavirin tablets in healthy Chinese volunteers was studied. A rapid and simple high performance liquid chromatography （HPLC） method was developed to determine the ribavirin concentration in human plasma. C18 column was used for separation with a column temperature of 25℃, the mobile phase was ultrapure water adjusted to pH 3 with acetic acid at the flow rate of 1 mL/min, and the detection wavelength was set at 207 rim. The linear range of the standard curves was 50.4-2016.0 ng/mL and the lower limit of quantification （LLOQ） was 50.4 ng/mL. The relative recoveries of ribavirin were more than 90% in plasma. The RSD of the intra-day precision was less than 10% and that of inter-day was less than 15%. The pharmacokinetic parameters of ribavirin were calculated by WinNonlin. Results indicated that the two-compartment model was a better model for describing the pharmacokinetics profile of ribavirin than one-compartment model. The AUC0-t was 10807.8 h.ng/mL, the CL/F was 64879.5 mL, and the Cmax was 525.1 ng/mL. These results provided the experimental data for the development of ribavirin dosage form.展开更多
Background A patented remote controlled capsule （RCC） has recently been developed to provide noninvasive drug delivery to selected sites in the human gut that allows assessment of regional gastrointestinal （GI） dr...Background A patented remote controlled capsule （RCC） has recently been developed to provide noninvasive drug delivery to selected sites in the human gut that allows assessment of regional gastrointestinal （GI） drug absorption under a normal physiological environment. The objective of this study was to investigate the rate and extent of aminophylline absorption after site-specific delivery of the drug in the GI tract using RCC and a magnetic marker monitoring （MMM） technique. Methods This study was conducted in twelve healthy male subjects, in a three-treatment, randomized, crossover manner with a 7-day washout. Eligible subjects received a 150 mg aminophylline dose through an oral administration, or via a remote controlled capsule, delivered to the small bowel or ascending colon. MMM was employed to monitor the GI transit of the RCC, and the radio-frequency signal was used to activate capsules at target sites. Blood samples were obtained at regular intervals until 24 hours post dose/activation. Plasma theophylline concentrations were measured by a TDx~ System Analyzer. A comparison of the PK profile with the oral dosing route of aminophylline was performed after delivery to the small bowel and colon. Results The RCC was well tolerated in volunteers. The mean capsule activation time for the small bowel and ascending colon was 2.07 hours and 6.08 hours post dose. Aminophylline had similar absorption profiles from the small bowel compared with the stomach, with an area under the curve （AUCt） ratio of 92% vs. the stomach, but a lower absorption profile from the ascending colon, with an AUCt ratio of 47.2% vs. the stomach. Conclusions The proprietary of the RCC and MMM technique offer the opportunity to obtain data on the intestinal absorption of a drug in humans under noninvasive conditions. Aminophylline is rapidly and efficiently absorbed from the small bowel. While colonic absorption was limited by the poor water condition although effective absorption was observed from the ascending colon. This provides an opportunity for rational development of modified-release formulations as well as alternative dosage forms.展开更多
Leukovir, an enteric-coated tablet, is the original drug product for internal use. The well-known nucleosides cladribine and ribavirin are the active ingredients of the drug product leukovir. Pharmacokinetic parameter...Leukovir, an enteric-coated tablet, is the original drug product for internal use. The well-known nucleosides cladribine and ribavirin are the active ingredients of the drug product leukovir. Pharmacokinetic parameters of the drug product for the internal use of leukovir active ingredients have been established. The cladribine half-absorption period was t<sub>1/2a</sub> = 49.5 h, C<sub>0</sub> = 276.4 μg/ml, C<sub>max</sub> = 6.0 μg/ml. Distribution and accumulation parameters (V<sub>d</sub>, V<sub>ss</sub> and AUC) have indicated that the drug distribution between the blood cells and blood plasma takes place in the same way, irrespective of the dosage form. Cladribine half-life period is t<sub>1/2e</sub> = 0.62 hours. The molecule total clearance and average lifetime in the body in the case of subcutaneous drug administration are approximately the same. Ribavirin is characterized by a half-absorption period of t<sub>1/2a</sub> = 0.71 h, C<sub>0</sub> = 115.6 μg/ml and C<sub>max</sub> = 75.5 μg/ml. Ribavirin total volume of distribution (V<sub>d</sub> = 1.3 l/kg) and stationary volume of distribution (V<sub>ss</sub> = 1.64 l/kg) were practically similar to leukovir when administered subcutaneously. The AUC value = 504.2 μg h/ml, which is 2.5 times less than that in the case of drug form administration. Leukovir was regarded as slightly toxic in an acute toxicity study. The risk of cumulation for this drug product is low.展开更多
文摘The clinical pharmacokinetics of ribavirin after a single oral dose of 600 mg ribavirin tablets in healthy Chinese volunteers was studied. A rapid and simple high performance liquid chromatography （HPLC） method was developed to determine the ribavirin concentration in human plasma. C18 column was used for separation with a column temperature of 25℃, the mobile phase was ultrapure water adjusted to pH 3 with acetic acid at the flow rate of 1 mL/min, and the detection wavelength was set at 207 rim. The linear range of the standard curves was 50.4-2016.0 ng/mL and the lower limit of quantification （LLOQ） was 50.4 ng/mL. The relative recoveries of ribavirin were more than 90% in plasma. The RSD of the intra-day precision was less than 10% and that of inter-day was less than 15%. The pharmacokinetic parameters of ribavirin were calculated by WinNonlin. Results indicated that the two-compartment model was a better model for describing the pharmacokinetics profile of ribavirin than one-compartment model. The AUC0-t was 10807.8 h.ng/mL, the CL/F was 64879.5 mL, and the Cmax was 525.1 ng/mL. These results provided the experimental data for the development of ribavirin dosage form.
文摘Background A patented remote controlled capsule （RCC） has recently been developed to provide noninvasive drug delivery to selected sites in the human gut that allows assessment of regional gastrointestinal （GI） drug absorption under a normal physiological environment. The objective of this study was to investigate the rate and extent of aminophylline absorption after site-specific delivery of the drug in the GI tract using RCC and a magnetic marker monitoring （MMM） technique. Methods This study was conducted in twelve healthy male subjects, in a three-treatment, randomized, crossover manner with a 7-day washout. Eligible subjects received a 150 mg aminophylline dose through an oral administration, or via a remote controlled capsule, delivered to the small bowel or ascending colon. MMM was employed to monitor the GI transit of the RCC, and the radio-frequency signal was used to activate capsules at target sites. Blood samples were obtained at regular intervals until 24 hours post dose/activation. Plasma theophylline concentrations were measured by a TDx~ System Analyzer. A comparison of the PK profile with the oral dosing route of aminophylline was performed after delivery to the small bowel and colon. Results The RCC was well tolerated in volunteers. The mean capsule activation time for the small bowel and ascending colon was 2.07 hours and 6.08 hours post dose. Aminophylline had similar absorption profiles from the small bowel compared with the stomach, with an area under the curve （AUCt） ratio of 92% vs. the stomach, but a lower absorption profile from the ascending colon, with an AUCt ratio of 47.2% vs. the stomach. Conclusions The proprietary of the RCC and MMM technique offer the opportunity to obtain data on the intestinal absorption of a drug in humans under noninvasive conditions. Aminophylline is rapidly and efficiently absorbed from the small bowel. While colonic absorption was limited by the poor water condition although effective absorption was observed from the ascending colon. This provides an opportunity for rational development of modified-release formulations as well as alternative dosage forms.
文摘Leukovir, an enteric-coated tablet, is the original drug product for internal use. The well-known nucleosides cladribine and ribavirin are the active ingredients of the drug product leukovir. Pharmacokinetic parameters of the drug product for the internal use of leukovir active ingredients have been established. The cladribine half-absorption period was t<sub>1/2a</sub> = 49.5 h, C<sub>0</sub> = 276.4 μg/ml, C<sub>max</sub> = 6.0 μg/ml. Distribution and accumulation parameters (V<sub>d</sub>, V<sub>ss</sub> and AUC) have indicated that the drug distribution between the blood cells and blood plasma takes place in the same way, irrespective of the dosage form. Cladribine half-life period is t<sub>1/2e</sub> = 0.62 hours. The molecule total clearance and average lifetime in the body in the case of subcutaneous drug administration are approximately the same. Ribavirin is characterized by a half-absorption period of t<sub>1/2a</sub> = 0.71 h, C<sub>0</sub> = 115.6 μg/ml and C<sub>max</sub> = 75.5 μg/ml. Ribavirin total volume of distribution (V<sub>d</sub> = 1.3 l/kg) and stationary volume of distribution (V<sub>ss</sub> = 1.64 l/kg) were practically similar to leukovir when administered subcutaneously. The AUC value = 504.2 μg h/ml, which is 2.5 times less than that in the case of drug form administration. Leukovir was regarded as slightly toxic in an acute toxicity study. The risk of cumulation for this drug product is low.
