Pharmacokinetics of amphotericin B lipid complex in critically ill patients undergoing continuous venovenous haemodiafiltration. 2013

Maeve E Malone, and Owen I Corrigan, and Pierce V Kavanagh, and Caitriona Gowing, and Maria Donnelly, and Deirdre M D'Arcy
School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.

The objective of this study was to examine the effect of continuous venovenous haemodiafiltration (CVVHDF) on the pharmacokinetics of amphotericin B (AmB) in critically ill patients following administration of amphotericin B lipid complex (ABLC). Plasma and ultrafiltrate (UF) samples were collected from patients administered ABLC and either receiving or not receiving CVVHDF. Pharmacokinetic (PK) analysis was performed on eight profiles from patients receiving CVVHDF and six profiles from patients not receiving CVVHDF. For patients receiving CVVHDF, the following median PK data were calculated: area under the concentration-time curve (AUC) = 13.9 h·μg/mL, volume of distribution at steady state (V(ss)) = 1476L and drug clearance (CL) = 27.4 L/h; for patients not receiving CVVHDF, the corresponding median PK data were 11.5 h μg/mL, 2048 L and 43.7 L/h, respectively. The median half-lives calculated during the dosage interval (t(1/2int)) were 30.9 h and 32.5 h on and off CVVHDF, respectively, and the total range of t(1/2int) values was 15.6-180.4 h. Observed median peak concentrations on Day 1 were 0.563 μg/mL and 0.468 μg/mL in patients on and off CVVHDF, respectively. From AmB present in the UF, clearance via CVVHDF contributed<1% of total plasma clearance. The AmB concentration-time profiles for patients administered ABLC on and off CVVHDF were compared and no statistically significant differences in AUC, CL, t(1/2int) and V(ss) were observed. In conclusion, CVVHDF had no clinically significant effect on the pharmacokinetics of AmB following administration of ABLC.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D010949 Plasma The residual portion of BLOOD that is left after removal of BLOOD CELLS by CENTRIFUGATION without prior BLOOD COAGULATION. Blood Plasma,Fresh Frozen Plasma,Blood Plasmas,Fresh Frozen Plasmas,Frozen Plasma, Fresh,Frozen Plasmas, Fresh,Plasma, Blood,Plasma, Fresh Frozen,Plasmas,Plasmas, Blood,Plasmas, Fresh Frozen
D005260 Female Females
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000666 Amphotericin B Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela. Amphocil,Amphotericin,Amphotericin B Cholesterol Dispersion,Amphotericin B Colloidal Dispersion,Fungizone
D000935 Antifungal Agents Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. Anti-Fungal Agents,Antifungal Agent,Fungicides, Therapeutic,Antibiotics, Antifungal,Therapeutic Fungicides,Agent, Antifungal,Anti Fungal Agents,Antifungal Antibiotics
D016638 Critical Illness A disease or state in which death is possible or imminent. Critically Ill,Critical Illnesses,Illness, Critical,Illnesses, Critical

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