Simultaneous Determination of Metoprolol and α-Hydroxymetoprolol in Human Plasma and Urine by Liquid Chromatography with a Preliminary Observation on Metoprolol Oxidation in Japanese Subjects

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Abstract
The elimination of gentamicin (G) was studied in 103 neonates (30 premature) during the first month of life after 2.5 mg/kg i.v. (as infusion) over 20–30 min. G plasma levels, measured by EMIT assay, were obtained before and at 1, 2, 3, and 6 h after infusion. We derived individual first-order kinetic parameters and designed optimal dose regimens. G plasma clearance, half-life, and recommended dose (mg/kg/h) changed exponentially with postnatal age during the first 14 days of life. No significant changes in kinetic values were noted during the first 3 days of life; however, they varied linearly with gestational age when they were measured during this period. Apgar score at 10 min and blood urea nitrogen significantly influenced the same parameters. The predictive value of a designed dose regimen was evaluated at steady-state, after dosage adjustment using two plasma concentration values: the minimum plasma concentration was below 2 mg/L in 93% of the patients; the plasma concentration observed within 1 h after completion of the infusion was (mean \pm SD) 5.33 \pm 0.97 mg/L. Our data suggest that 2.5 mg/kg every 12 h is appropriate in most neonates except for 0–2-day-old premature infants who require 2.5 mg/kg every 18 h. Monitoring of G plasma levels is advisable in infants with low Apgar score and/or renal failure.