Pediatric pharmacology (New York, N.Y.)最新文献

Aminosides lead to a well-known nephrotoxicity. The possibility of the developing kidney being altered in utero after the pregnant mother's administration has been investigated. We gave gentamicin (75 mg/kg/day) to pregnant rats during periods of organogenesis (days 7-11) and the beginning of glomeruli differentiation (days 14-18). A group of nonpregnant females was also treated for the same period and at the same time each day. Gentamicin-treated mothers presented only minor modifications of the blood biology with no acute renal failure when treated nonpregnant females have a hypercreatininemia. The deep cortical area, containing the fully formed nephrons of neonates, presented less glomeruli that were differentiated in the gentamicin group than in the control group. Moreover with both light and electron microscopy, glomeruli and proximal tubules showed evidences of nephrotoxicity in the juxtamedullary cortex. This finding of an in utero aminoside nephrotoxicity demonstrates the possible toxicity of gentamicin on fetus kidneys when given during the pregnancy.

Serum concentration of dantrolene and its active metabolite, 5-hydroxydantrolene were determined in 27 cerebral palsy patients. Correlation coefficients between the oral dose of dantrolene and serum levels of dantrolene and its major metabolite, 5-hydroxydantrolene were rather small in cerebral palsy patients. The mean half-times of dantrolene and 5-hydroxydantrolene were 3.41 (n = 6) and 4.00 (n = 5) hours, respectively. These values were about a half of those reported earlier [Lietman et al., 1974; Meyler et al., 1979; Flewellen et al., 1983]. The poor correlation between serum level and dose may be due to the variation in an extent of oral dantrolene availability.

Medical students, pediatric residents, and pediatricians were asked to evaluate the cost of commonly prescribed medications. Their estimations varied considerably and were considered as adequate in 40%, 52%, and 62% of the cases, respectively. In most situations, the adequacy of their estimations did not seem to improve significantly with the length of training and practice. Since the cost of medications may influence compliance, it should probably be discussed more often during the course of medical and pediatric training.

Two adolescents with serum theophylline concentrations in excess of 100 mg/L were treated with continuous nasogastric infusion of activated charcoal after an intentional overdose. In both cases, nasogastric boluses of 20 to 50 gm of charcoal resulted in prompt emesis of stomach contents despite the presence of a functional nasogastric tube. For nasogastric infusion, activated charcoal was diluted in 0.9% sodium chloride and infused at a rate of 0.25 to 0.5 gm/kg/hr up to a maximal rate of 50 gm/hr. Despite the high initial serum concentrations, the theophylline elimination half-lives during the first 20 hours after the start of charcoal were 7.7 and 13.5 hours. Subsequently, this decreased to 2.6 and 3.2 hours. No serious neurologic, cardiovascular, or metabolic derangements were observed. Continuous nasogastric infusions of activated charcoal may be safe and effective alternatives to charcoal hemoperfusion in patients with theophylline overdose.

The single-dose pharmacokinetics of two dosages of imipenem-cilastatin (1:1), 10 and 25 mg/kg, were studied in ten children. Plasma concentrations, half-lives, and areas under the curve of both imipenem and cilastatin was significantly greater at the 25 mg/kg dosage but the half-lives and clearances of the two drugs were similar to each other only at the larger dose. After a 25 mg/kg dose, the mean peak and trough (6 hr) plasma concentrations of imipenem were 78.8 and 0.68 micrograms/ml, respectively, and the half-lives of imipenem and cilastatin were 1.12 and 0.97 hr, respectively. Urinary excretion of imipenem was 43-47% during the 6 hr following administration of either dosage. No clinical or laboratory toxicity was noted. A 25 mg/kg dose of imipenem-cilastatin maintains serum concentrations of imipenem above the minimum inhibitory concentration (MIC) of potential pathogens for 4-6 hr and seems appropriate for multiple-dose studies. Our data suggest that a minimum dosage, greater than 10 mg/kg, of cilastatin may be required to prolong the half-life of imipenem to adult values.

We studied 12 newborn infants (gestational ages 26-39 wk [mean +/- SD, 30.6 +/- 4.7]; birth weight 640-2700 g, [mean, 1,322 +/- 688]; postnatal age 1-24 days [mean, 9.6 +/- 8.5]) who received clindamycin phosphate for suspected or proven necrotizing enterocolitis (ten patients) or suspected anaerobic septicemia (two patients) in doses of 3.2-11 mg/kg every six hours. Range of mean serum concentration of clindamycin at steady state was between 12.7 and 40 micrograms/ml (therapeutic range = 2-10 micrograms/ml). High concentrations could be attributed to elimination T1/2 (6.3 +/- 2.1 hr) 100% longer than in older children or adults. Clindamycin clearance (61.6 +/- 31.6 hr ml/kg/hr) was lower than in older children or adults. Because of the observed prolongation in T1/2 and correspondingly lower clearance, the IV dose of clindamycin in newborn infants should be reduced to 15-20 mg/kg/day given in four daily doses.

The purpose of this study was to test the hypothesis that nifedipine when given with dopamine will lower pulmonary vascular resistance in hypoxic lambs without altering systemic vascular resistance. We studied six unanesthetized lambs (ranging in age from 13 to 35 days) as they breathed air or on a separate day as they breathed 10% O2 and 3% CO2 in nitrogen. First, we infused dopamine at progressively higher rates (10, 20, 40, 80, and 160 micrograms/kg/min) while measuring mean aortic, pulmonary arterial, and left atrial pressures and heart rate continuously and cardiac output and arterial blood gas tensions at frequent intervals. Then, while maintaining the dopamine infusion at 160 micrograms/kg/min, we infused boluses of nifedipine intravenously (10 micrograms/kg) every 5 min until a cumulative dose of 50 micrograms/kg had been administered. In both groups of lambs, cardiac output increased with increasing rates of dopamine infusion (baseline to maximum dopamine: 260 +/- 20 ml/kg/min to 420 +/- 60 ml/kg/min for normoxic lambs and 400 +/- 50 ml/kg/min to 560 +/- 80 ml/kg/min for hypoxic lambs). While systemic vascular resistance and pulmonary vascular resistance did not change significantly in either group during dopamine infusion, the ratio of pulmonary vascular resistance to systemic vascular resistance increased at low rates of infusion and decreased at high rates. The peak in this ratio occurred at a rate of infusion of 20-40 micrograms/kg/min in normoxic lambs and 40-80 micrograms/kg/min in hypoxic lambs. Infusion of nifedipine did not affect cardiac output in normoxic lambs but decreased it significantly in hypoxic lambs. Nifedipine infusion did not affect pulmonary vascular resistance in the normoxic lambs and increased pulmonary vascular resistance in the hypoxic lambs. We conclude that nifedipine, even when given with high doses of dopamine, is not a specific pulmonary vasodilator.

The effect of ritodrine hydrochloride (RH) on bilirubin metabolism in newborn Wistar rats was studied. Wistar rat pups were given two 35-mg/kg injections of RH, and total bilirubin formation (TBF) was determined from the whole body excretion rate of carbon monoxide (VeCO). Early labeled bilirubin formation (ELB), plasma bilirubin levels, and hepatic heme oxygenase (HO) activity were also determined. We found significant increases in TBF, ELB, and HO in the RH-treated animals over the control animals. These increases, however, were small, considering the high doses of RH administered. Our findings suggest that at clinically administered doses, the potential for RH to exacerbate neonatal jaundice is minimal.

Increased serum lipid peroxide (LPO) and decreased vitamin E (VE) levels have been reported in epileptic children after long-term anticonvulsant therapy. The present study was designed to examine the acute effects of phenobarbital (PB) on lipid peroxidation in VE deficient rats. Five-day treatment with PB (75 mg/kg/day, IP) caused a significant increase in liver LPO levels (P less than 0.01), a decrease in plasma LPO levels (P less than 0.02), and a significant decrease in liver VE levels (P less than 0.05). It is suggested that PB plays an important role in lipid peroxidation in the liver by interfering with VE metabolism.

Multiple-dose kinetics of digoxin were studied over a 7-day period in five neonates receiving intravenous digoxin therapy (one initial digitalizing dose followed by single daily doses). Their weights ranged from 1.04 to 2.68 kg (means = 1.61 kg), gestational ages from 28 to 39 weeks (means = 31.8 weeks), and postnatal ages from 2 to 19 days (means = 8.0 days). The 24-hour serum digoxin levels and urinary creatinine and digoxin excretion after the 1st and 7th doses on days 1 and 7 were employed to derive the kinetic parameters. Values of each following parameter (mean +/- SD) were obtained on days 1 and 7, respectively: (1) creatinine clearance (ml/min/1.73 m2) 12 +/- 6, 13 +/- 8; (2) renal digoxin clearance (ml/min/1.73 m2) 13 +/- 8, 15 +/- 10; (3) total body digoxin clearance (ml/min/1.73 m2) 35 +/- 14, 39 +/- 24; (4) volume of distribution (L/kg) 7.2 +/- 1.0, 6.9 +/- 1.1; and (5) half-life (hours) 48 +/- 19, 49 +/- 27. No consistent changes of the above kinetic parameters from days 1 to 7 were observed in these five neonates (P greater than 0.05, paired student's t-test).