Pharmacokinetics of ribavirin granules

Domestic research data of human bioavailability show that ribavirin granules is absorbed rapidly after oral administration, and its blood concentration can reach the peak within 60-90 minutes. After ribavirin enters the body, it is phosphorylated to produce an active metabolite-ribavirin monophosphate. The elimination half-life is about 24 hours. Ribavirin can stay in red blood cells. It is mainly excreted by the kidneys, and only a small amount is excreted with feces. According to the Physician's Desk Reference (54th edition), the pharmacokinetics of single dose and multiple doses of ribavirin in patients with chronic hepatitis are summarized in Table 1. Ribavirin is absorbed quickly and completely after oral administration. However, due to the first-pass effect, the average absolute bioavailability was 64%(44). In the dose range of 200 ~ 1200mg, the dose of ribavirin has a linear relationship with AUC0-t (AUC from 0: 00 to the last test point). The relationship between dose and Cmax is curvilinear, and tends to be asymptotic when the single dose is above 400 ~ 600 mg. After repeated oral administration, it was observed that ribavirin accumulated 6 times in plasma (based on AUC 12 hours). After continuous oral administration of 600mg twice a day, it can reach a stable state in about four weeks. The steady-state average plasma concentration was 2200(37%)ng/ml, and the average half-life measured after drug withdrawal was 298(30%) hours, indicating that this product may be slowly eliminated from the non-plasma part. Effect of food on the absorption of ribavirin: In the single-dose drug study, when ribavirin was taken together with a high-fat diet (84 1 kcal, 53.8g of fat, 31.6g of protein and 57.4g of sugar), AUCtf and Cmax increased by 70%. There is not enough data to confirm the clinical relevance of these results. There is no explanation about food consumption in clinical efficacy research. (See Usage and Dosage) Effect of antacids on the absorption of ribavirin: Taking an antacid containing magnesium, aluminum and dimethicone at the same time with ribavirin will lead to a decrease of the average AUCtf of ribavirin by 65,438 04%. The clinical relevance of single dose study results is unknown. [See table 1] Ribavirin can enter red blood cells, which has been confirmed to enter through es-type nucleoside carrier. This type of vector exists in almost all types of cells, which can lead to the expansion of distribution volume. Ribavirin rarely binds to plasma proteins. Ribavirin has two metabolic pathways: (i) reversible phosphorylation in nucleated cells; (ii) The other is a metabolic pathway including debromination and amine hydrolysis to produce tripyrrole carboxylic acid metabolites. Ribavirin and its tripyrrole amide and tripyrrole carboxylic acid metabolites are excreted through the kidney. After oral administration of 600mg 14C- ribavirin, about 6 1% of urine and 12% of feces were eliminated within 336 hours, of which only 17% was unconverted ribavirin. The results of in vitro metabolism of human and rat liver microsomes show that ribavirin is rarely or hardly metabolized by cytochrome P450, and there are only a few potential enzyme-drug interactions. Renal insufficiency in special population: After a single dose of ribavirin (400mg) was given to HCV infected patients with different degrees of renal insufficiency, the creatinine clearance rate 10 ~ 30 ml/min was 3 times higher than that of the control group (creatinine clearance rate 90 ml/min) and 2 times higher than that of patients with creatinine clearance rate 30 ~ 60 ml/min. It is difficult to predict the pharmacokinetic parameters of ribavirin after multiple doses. Hemodialysis can not effectively remove ribavirin. Ribavirin is not recommended for patients with creatinine clearance rate [50 ml/min] (see precautions). Abnormal liver function: The patients with mild, moderate and severe liver dysfunction (A, B and C according to Chaild-pugh classification) had no significant difference in average AUCtf value compared with the control group after taking a single dose (600mg) of ribavirin orally. However, the average Cmax value increased with the severity of liver function damage, and the Cmax value of patients with severe liver function damage was twice that of the control group. Pediatric patients: No detailed pharmacokinetic study has been conducted on pediatric patients. Elderly patients: Pharmacokinetics of elderly patients has not been studied. Sex: In the single-dose study of male patients with 18 and female patients with 18, no obvious difference in gender pharmacokinetics was found.