OBJECTIVE: To find a dose of fluconazole for very low birth weight infants during an outbreak of Candida parapsilosis. METHODS: Twelve premature infants (mean gestational age, 27.4 weeks; mean birth weight, 912 gm) receiving fluconazole prophylactically from the first day of life were enrolled in an open phase I-II pharmacokinetics, safety, and tolerance trial. Up to 5 doses of 6 mg/kg were administered intravenously every 72 hours during the first 2 weeks of life. Pharmacokinetic characteristics of fluconazole were determined after the first, third, and fifth doses. RESULTS: The mean peak and trough concentrations after the 3 doses were 5.5 and 2.6 micrograms/ml, 12.8 and 4.3 micrograms/ml, and 10.0 and 2.9 micrograms/ml (p = 0.0002 and p = 0.07), respectively. The mean fluconazole half-lives were 88.6 hours (n = 7), 67.5 hours (n = 9), and 55.2 hours (n = 4; p = 0.3). The mean total clearance corrected for weight (CL/kg) was 0.18 ml/min/kg (n = 7), 0.33 ml/min/kg (n = 7), and 0.52 ml/min/kg (n = 4; p = 0.02), and the mean volume of distribution 1.18 L/kg (n = 7), 1.84 L/kg (n = 7), and 2.25 L/kg (n = 4; p = 0.05). Weight-corrected clearance increased with postnatal age (r = 0.61; p = 0.007). CONCLUSIONS: With the used fluconazole dose (6 mg/kg every 3 days), the mean serum peak and trough concentrations increased during the first week but decreased during the second week. After the first week we suggest a dose of 6 mg/kg every 2 days, or even daily.
OBJECTIVE: To find a dose of fluconazole for very low birth weight infants during an outbreak of Candida parapsilosis. METHODS: Twelve premature infants (mean gestational age, 27.4 weeks; mean birth weight, 912 gm) receiving fluconazole prophylactically from the first day of life were enrolled in an open phase I-II pharmacokinetics, safety, and tolerance trial. Up to 5 doses of 6 mg/kg were administered intravenously every 72 hours during the first 2 weeks of life. Pharmacokinetic characteristics of fluconazole were determined after the first, third, and fifth doses. RESULTS: The mean peak and trough concentrations after the 3 doses were 5.5 and 2.6 micrograms/ml, 12.8 and 4.3 micrograms/ml, and 10.0 and 2.9 micrograms/ml (p = 0.0002 and p = 0.07), respectively. The mean fluconazole half-lives were 88.6 hours (n = 7), 67.5 hours (n = 9), and 55.2 hours (n = 4; p = 0.3). The mean total clearance corrected for weight (CL/kg) was 0.18 ml/min/kg (n = 7), 0.33 ml/min/kg (n = 7), and 0.52 ml/min/kg (n = 4; p = 0.02), and the mean volume of distribution 1.18 L/kg (n = 7), 1.84 L/kg (n = 7), and 2.25 L/kg (n = 4; p = 0.05). Weight-corrected clearance increased with postnatal age (r = 0.61; p = 0.007). CONCLUSIONS: With the used fluconazole dose (6 mg/kg every 3 days), the mean serum peak and trough concentrations increased during the first week but decreased during the second week. After the first week we suggest a dose of 6 mg/kg every 2 days, or even daily.
Authors: J H Rex; M A Pfaller; T J Walsh; V Chaturvedi; A Espinel-Ingroff; M A Ghannoum; L L Gosey; F C Odds; M G Rinaldi; D J Sheehan; D W Warnock Journal: Clin Microbiol Rev Date: 2001-10 Impact factor: 26.132
Authors: K C Wade; D Wu; D A Kaufman; R M Ward; D K Benjamin; J E Sullivan; N Ramey; B Jayaraman; K Hoppu; P C Adamson; M R Gastonguay; J S Barrett Journal: Antimicrob Agents Chemother Date: 2008-09-22 Impact factor: 5.191
Authors: Gudrun Würthwein; Andreas H Groll; Georg Hempel; Felice C Adler-Shohet; Jay M Lieberman; Thomas J Walsh Journal: Antimicrob Agents Chemother Date: 2005-12 Impact factor: 5.191