Abstract. The assumed metabolic breakdown of albendazole by mucosal CYP3A4 enzymes was studied by coadministering albendazole (10 mg/kg) with grapefruit juice. Concentrations of albendazole sulfoxide (ABZSX), the active metabolite of albendazole, were compared with those after albendazole was administered with water, a fatty meal, or grapefruit juice plus cimetidine (10 mg/kg). In comparison to water, maximum ABZSX concentration (C max ) was enhanced 6.5-fold by a fatty meal (from 0.24 ± 0.09 mg/l to 1.55 ± 0.30 mg/l; mean ± SD; P < 0.001) and 3.2-fold by grapefruit juice (from 0.24 ± 0.09 mg/l to 0.76 ± 0.37 mg/L; P ‫ס‬ 0.031). When grapefruit juice was combined with cimetidine, C max was significantly lower than with grapefruit juice alone (0.41 ± 0.29 mg/l and 0.76 ± 0.37 mg/l, respectively; P ‫ס‬ 0.022). The area under the concentration-time curve from 0 to infinity (AUC 0-⍀ ) followed a comparable pattern. Half-life (T 1/2 ) was 8.8 ± 4.2 hr and 8.2 ± 4.3 hr after administration with water or a fatty meal (P ‫ס‬ 1.000). Grapefruit juice shortened T 1/2 by 46% (P ‫ס‬ 0.026). We hypothesize that albendazole is metabolized by CYP3A4 enzymes in the intestinal mucosa. This process can be inhibited by grapefruit juice. Cimetidine decreased albendazole bioavailability.

Abstract. The low bioavailability of albendazole affects the therapeutic response in patients with echinococcosis. Cimetidine co-administration is reported to improve bioavailability. To analyze the assumed dose-dependent bioavailability of albendazole, we administered 5 to 30 mg/kg albendazole to 6 male volunteers in a randomized cross-over study. To assess the effect of cimetidine (10 mg/kg twice daily), the drug was given with albendazole (20 mg/kg). A dose-dependent bioavailability was not observed. This was due to inter-individual variability of the maximal concentration (C max 38%-72%) of albendazole sulphoxide (ABZSX), the active metabolite of albendazole. C max was 0.21 Ϯ 0.14 mg/L after 5 mg/kg and 0.39 Ϯ 0.19 mg/L after 30 mg/kg albendazole (P ϭ 0.217). Cimetidine tended to decrease C max by 52% (P ϭ 0.109) and significantly inhibited ABZSX breakdown as indicated by the prolongation of ABZSX elimination half-life from 7.4 Ϯ 3.3 hr to 19.0 Ϯ 11.7 hr (P ϭ 0.028). Remarkably, the inter-individual variability of C max was significantly lower during cimetidine co-administration: 14% versus 72%.

Background: Surgery is the treatment of choice in echinococcal cysts with cystobiliary fistulas. PAIR (puncture, aspiration, injection, and reaspiration of scolecidals) is contraindicated in these cases. Aim: To evaluate a modified PAIR method for percutaneous treatment of multivesicular echinococcal cysts with or without cystobiliary fistulas which contain non-drainable material. Patients: Twelve patients were treated: 10 patients with multivesicular cysts which contained non-drainable material and were complicated by spontaneous intrabiliary rupture, secondary cystobiliary fistulas, cyst infection, or obstructed portal or hepatic veins; and two patients with large univesicular cysts and a ruptured laminated membrane, one obstructing the portal and hepatic veins and one a suspected cystobiliary fistula. Methods: The methods used, termed PEVAC (percutaneous evacuation of cyst content), involved the following steps: ultrasound guided cyst puncture and aspiration of cyst fluid to release intracystic pressure and thereby to avoid leakage; insertion of a large bore catheter; aspiration and evacuation of daughter cysts and endocyst by injection and reaspiration of isotonic saline; cystography; injection of scolecidals only if no cystobiliary fistula was present; external drainage of cystobiliary fistulas combined with endoprosthesis or sphincterotomy; catheter removal after complete cyst collapse and closure of the cystobiliary fistula. Results: In all 12 patients initial cyst size was 13.1 (6-20) cm (mean (range)). At follow up 17.9 (4-30) months after PEVAC, seven cysts had disappeared and five cysts had decreased to 2.4 (1-4) cm (p=0.002). In eight patients with multivesicular cysts, a cystobiliary fistula, and infection, cyst size was 12.5 (6-20) cm, catheter time 72.3 (28-128) days, and hospital stay 38.1 (20-55) days. At 17.3 (4-28) months of follow up, six cysts had disappeared and in two cysts residual size was 1 and 2.9 cm, respectively (p=0.012). In four patients without a cystobiliary fistula, cyst size was 14.4 (12.7-16) cm, catheter time 8.8 (3-13) days, and hospital stay 11.5 (8-14) days. At 19.3 (9-30) months of follow up, one cyst had disappeared and three cysts were 85 (69-94)% smaller (2.2 (1-4) cm) (p=0.068). Conclusion: PEVAC is a safe and effective method for percutaneous treatment of multivesicular echinococcal cysts with or without cystobiliary fistulas which contain non-drainable material.

No abstract

No abstract