Pharmacokinetics of once-daily dosing of gentamicin in neonates.

In a prospective, randomized trial of once-daily versus twice-daily intravenous or intramuscular dosing with gentamicin, 11 neonates received 5.0 mg/kg once daily and 15 received 2.5 mg/kg twice daily for 2 ro 3 days. The once-daily intravenous dosing group and the twice-daily intravenous or intramuscular dosing group, respectively, had mean steady-state gentamicin peak concentrations of 10.7 versus 6.6 micrograms/ml (p < 0.05), 6-hour postdosing concentrations of 4.7 versus 2.8 micrograms/ml (p < 0.05), trough concentrations of 1.7 versus 1.7 micrograms/ml, elimination half-life of 8.8 versus 5.4 hours (p < 0.05), and volume of distribution at steady state of 0.67 versus 0.46 L/kg. No nephrotoxic effects were identified in any group. Once-daily gentamicin therapy with 5.0 mg/kg in neonates achieves peak serum levels that are more suitable for optimal bacterial killing than those which traditional regimens achieve. Similar trough levels suggest that even larger doses and longer dosing intervals may be ideal in term neonates.

Principles of drug transfer into breast milk and drug disposition in the nursing infant.

There are numerous factors to consider when assessing the safety of drugs in lactating women. Drug properties facilitating transfer into milk as well as the pharmacokinetic properties of the drug in the mother and infant must be evaluated. Drug properties which promote low milk concentrations are: large volume of distribution, high protein binding, low lipid solubility, ionization at physiologic pH and large molecular weight. Following transfer into breast milk, drugs with low bioavailability and short elimination half-lives in neonates have improved safety.

Antidepressant use during breastfeeding.

Women who suffer from postpartum depression require treatment. Caution must be exercised if any antidepressant is used. These agents concentrate in the central nervous system; therefore, serum concentrations and breastmilk: plasma ratios may not accurately predict infant drug exposure. Since there is no absolute contraindication to breastfeeding during antidepressant use, recommendations should be made on a case-by-case basis limited to healthy term infants. When possible plasma antidepressant concentrations, including metabolites, should be measured in the infant. Frequent developmental follow-up, not only during the treatment period but throughout childhood, should be performed on these infants.

Pharmacokinetic evaluation of two theophylline dosing methods for infants.

Theophylline is often used in infants, yet few studies have evaluated the serum concentrations achieved with currently recommended dosing guidelines. Two theophylline dosing regimens, a postnatal age (PNA) equation and the Federal Drug Administration (FDA) dosing guidelines, were retrospectively evaluated in a group of infants, postconceptional age (PCA) 31-96 weeks, with known theophylline clearances. Large variations in theophylline concentrations were observed for both dosing regimens. Mean +/- SD projected steady-state theophylline serum concentrations, Css, were 17.7 +/- 7.6 micrograms/ml with the PNA equation (n = 40) and 5.6 +/- 2.9 micrograms/ml with the FDA guidelines (n = 52). Over one-third of Css with the PNA equation were > 20 micrograms/ml. Using the FDA guidelines, 40% of Css were < 5 micrograms/ml. The majority of infants < 40 weeks PCA attained projected Css > 20 micrograms/ml (21.7 +/- 5.1 micrograms/ml) with the PNA equation, but < 5 micrograms/ml (4.3 +/- 1.4 micrograms/ml) with FDA guidelines. An age-related bias was also observed for each dosing method. For the PNA equation, projected Css were significantly higher in infants < 40 weeks versus > or = 40 weeks PCA (21.7 +/- 5.1 versus 15.8 +/- 7.9 micrograms/ml, p < 0.01). For FDA guidelines, projected Css were significantly lower in infants < 40 weeks PCA versus older infants (4.3 +/- 1.4 versus 8.5 +/- 4.3 micrograms/ml, p < 0.001). Clinical application of currently accepted theophylline dosing guidelines for infants results in a high frequency of Css, which are potentially toxic or subtherapeutic.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of intravenous vancomycin in pediatric cardiopulmonary bypass surgery.

The purposes of this investigation were to characterize the disposition of vancomycin in children undergoing cardiopulmonary bypass (CPB) surgery and to determine whether a 15-mg/kg intravenous dose provides adequate serum concentrations during and after CPB. Six children (age range, 0.8 to 4.8 years) received intravenous vancomycin 15 mg/kg 1 to 2 hours before CPB surgery. Serial blood samples (mean, 10/patient) were collected before, during and after CPB surgery. The mean (+/- SD) vancomycin concentrations at the end of the infusion and 5 hours after the infusion were 27.3 +/- 5.7 and 5.9 +/- 3.0 mg/liter, respectively. The initiation of CPB resulted in an abrupt decrease (44.5%) in serum vancomycin concentrations; however, concentrations remained constant (range, 6.2 to 14.1 mg/liter) throughout the rest of the CPB procedure. The mean (+/- SD) values for the apparent volume of distribution, total body clearance and elimination half-life were 0.59 +/- 0.15 liter/kg, 2.94 +/- 0.93 ml/min/kg and 2.4 +/- 0.8 hours, respectively. These values were similar to those reported in the literature for children not undergoing CPB surgery. A single vancomycin dose of 15 mg/kg before pediatric CPB surgery provides serum concentrations greater than 5 mg/liter throughout the duration of the CPB procedure. To sustain these concentrations subsequent dosing of vancomycin is necessary within 6 hours after the initial vancomycin dose.