Pharmacokinetics, safety of a single dose and multiple doses of voriconazole injection of two formulations, in Chinese healthy volunteers

Abstract

Voriconazole is a first‐line medicine for treating invasive fungal infections. We evaluated the pharmacokinetics (PK) and safety of single/multiple doses of voriconazole injection of Hailing Pharmaceutical Group (Test, T), an imitation of Vfend® (Reference, R). Healthy subjects (n = 36) randomly received a once‐daily dose of T or R 3 or 4 mg/kg on Day 1 (single dose), a once‐daily dose of T or R 6 mg/kg on Day 4, and then six consecutive days for twice‐daily doses of T or R 3 or 4 mg/kg (multiple doses). The plasma was collected up to 72 h at time points after dosing on Day 1/10. Samples were measured by the liquid chromatography tandem mass spectrometry method. PK parameters were confirmed according to a non‐compartmental model. The relationship between the PK profiles of T and R revealed the different behavior in 3‐ and 4‐mg/kg groups. After single/multiple doses in the 3‐mg/kg group, the mean value for the area under the plasma concentration–time curve (AUC0−t, AUC0−∞) of R is about twice T. However, there was a high degree of similarity in the 4‐mg/kg group. The maximum plasma concentration (Cmax) of T and R showed no noticeable difference in the two groups. The median Tmax of T and R were within 2.0–2.13 h in the 3‐mg/kg group and 2.0–2.17 h in the 4‐mg/kg group. Severe adverse events did not occur. No clinically significant differences were found in safety and tolerance between T and R. This clinical study indicated that voriconazole injection might provide a safer alternative medicine.