Comparative pharmacokinetics of amphotericin B after single- and multiple-dose administration of G-ABCD and conventional amphotericin B deoxycholate to rats. (September 2020)

• Record Type: Journal Article
• Authors: Qi, Huanhuan; Zhang, Xueyuan; Feng, Hao; Xiong, Yating; Chen, Yuancheng; Zhang, Jing; Li, Chunlei
• Is Part Of: Journal of global antimicrobial resistance. Volume 22(2020)
• Page Start: 608
• Page End: 612
• Publication Date: 2020-09
• Subjects: Amphotericin B colloidal dispersion -- Amphotericin B -- Amphotericin B deoxycholate -- Pharmacokinetics -- Tissue distribution -- Rat; Drug resistance -- Periodicals; Drug resistance -- Periodicals; Drug resistance; Periodicals; 616.9041
• DOI: 10.1016/j.jgar.2020.05.011
• Languages: English
• ISSNs: 2213-7165

Abstract

Highlights: G-ABCD is a biosimilar product of amphotericin B colloidal dispersion. G-ABCD has pharmacokinetic advantages over amphotericin B deoxycholate in rats. Amphotericin B concentration reaches a steady state after seven doses of G-ABCD. G-ABCD provides lower but lasting plasma amphotericin B levels. Multiple-dose G-ABCD results in lower distribution and marginal accumulation in kidneys. Abstract: Objective: G-ABCD is a biosimilar product of amphotericin B colloidal dispersion (ABCD). This study was designed to systematically examine the plasma pharmacokinetics (PK) and tissue distribution of G-ABCD in rats, using amphotericin B deoxycholate (DAmB) as a positive control. Methods: Male Sprague-Dawley rats received single dose or 14 doses of G-ABCD (1.0, 2.0 or 5.0 mg/kg) or the conventional micellar formulation DAmB) (1.0 mg/kg) via intravenous injection. Plasma and tissue samples were obtained for analysis of amphotericin B concentration by liquid chromatography-tandem mass spectrometry. Results: After a single-dose administration of 1 mg/kg, G-ABCD resulted in a significantly lower plasma peak drug concentration (Cmax ) (1536 vs. 5256 ng/mL) and area under the curve from time 0 to ∞ (AUC0–∞ ) (3972 vs. 7006 h ng/mL) of non-complexed amphotericin B than DAmB. G-ABCD was associated with quicker distribution but slower elimination of amphotericin B than DAmB. Amphotericin B concentration reached a steady state after seven doses of G-ABCD. After multiple doses of 1 mg/kg, G-ABCD showed a lower peak level and longer half-life of amphotericin B in plasma than DAmB. G-ABCD treatment in rats was associated with relatively higher distribution to liver and spleen, but reduced amphotericin B delivery to kidneys, the major target organ of toxicity. Conclusion: These results suggest that G-ABCD provides a flatter but more lasting plasma level of amphotericin B and lower kidney burden in rats than DAmB.