Single-dose gabapentin pharmacokinetics and safety in healthy infants and children.

Gabapentin (Neurontin) is a gamma-aminobutyric acid analogue indicated in adults for adjunctive treatment of partial seizures with or without secondary generalization. Two studies were conducted to determine the single-dose pharmacokinetics of gabapentin in healthy subjects age 1 month to 12 years and to guide dose selection in safety and efficacy trials in pediatric patients. Forty-eight subjects were given single oral doses of gabapentin (10 mg/kg) while fasting. Enrollment was homogeneously distributed throughout the age range. Plasma samples were drawn predose and then serially for 24 hours postdose. Single doses of gabapentin were well tolerated by healthy pediatric subjects. Plots of pharmacokinetic parameters versus age suggested significant differences between younger (1 month to < 5 years) and older (> or =5 to 12 years) subjects. Mean area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) was 25.6 microg x h/mL in younger subjects and 36.0 microg x h/mL in older subjects (p < 0.001). Corresponding mean peak plasma concentrations (Cmax) were 3.74 and 4.52 microg/ml (p < 0.05). Oral clearance (normalized for body weight) was 7.40 and 4.41 mL/min/kg in younger subjects and older subjects, respectively (p < 0.001). It was concluded that children between 1 month and < 5 years of age require approximately 30% higher daily doses of gabapentin than those > or =5 to 12 years of age.

Aprotinin decreases exposure to allogeneic blood during primary unilateral total hip replacement.

BACKGROUND: Aprotinin, a hemostatic agent, regulates fibrinolysis, modulates the intrinsic coagulation pathway, stabilizes platelet function, and exhibits anti-inflammatory properties through inhibition of serine proteases, such as trypsin, plasmin, and kallikrein. Aprotinin has been used successfully for many years in cardiac operations, and there have been preliminary investigations of its use in hip replacement operations. The objectives of this multicenter, randomized, placebo-controlled, double-blind trial were to evaluate the efficacy and safety of aprotinin as a blood-sparing agent in patients undergoing an elective primary unilateral total hip replacement and to examine its effect on the prevalence of deep-vein thrombosis in this population. METHODS: Seventy-three patients received a placebo; seventy-six patients, a low dose of aprotinin (a load of 500,000 kallikrein inhibitor units [KIU]); seventy-five, a medium dose of aprotinin (a load of 1,000,000 KIU, with infusion of 250,000 KIU per hour); and seventy-seven patients, a high dose of aprotinin (a load of 2,000,000 KIU, with infusion of 500,000 KIU per hour). The end points for the determination of efficacy were transfusion requirements and blood loss. Patients received standard prophylaxis against deep-vein thrombosis and underwent compression ultrasonography with color Doppler imaging of the proximal and distal venous systems of both legs to evaluate for the presence of deep-vein thrombosis. RESULTS: Aprotinin reduced the percentages of patients who required any form of blood transfusion (47 percent of the patients managed with a placebo needed a transfusion compared with 28 percent of those managed with low-dose aprotinin [p = 0.02],27 percent of those managed with high-dose aprotinin [p = 0.008], and 40 percent of those managed with medium-dose aprotinin [p = 0.5]). Only 6 percent (twelve) of the 212 patients treated with aprotinin required allogeneic blood compared with 15 percent (ten) of the sixty-eight patients treated with the placebo (p = 0.03). Aprotinin decreased the estimated intraoperative blood loss (p = 0.02 for the low-dose group, p = 0.04 for the medium-dose group, and p = 0.1 for the high-dose group), the measured postoperative drainage volume (p = 0.4 for the low-dose group, p = 0.006 for the medium-dose group, and p = 0.000 for the high-dose group), and the mean reduction in the hemoglobin level on the second postoperative day (thirty-four grams per liter for the placebo group, twenty-eight grams per liter for the low-dose group [p = 0.000], twenty-six grams per liter for the medium-dose group [p = 0.000], and twenty-three grams per liter for the high-dose group [p = 0.0001). The rate of deep-vein thrombosis was similar for all groups. CONCLUSIONS: We concluded that aprotinin is safe and effective for use as a hemostatic agent in primary unilateral total hip replacements. In patients who are at high risk of receiving allogeneic blood, use of aprotinin may be of particular clinical and economic benefit.

Meropenem: a new carbapenem antimicrobial.

OBJECTIVE: To describe and then compare an investigational carbapenem antibiotic, meropenem, with the only currently available antibiotic in this class, imipenem/cilastatin. DATA IDENTIFICATION: An English language search using MEDLINE (1988-1993); Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), 1991; and Abstracts of the 32nd ICAAC, 1992. STUDY SELECTION: All current scientific publications were reviewed for study design and quality. Emphasis was placed on susceptibility and pharmacokinetic analysis. Phase 3 clinical trials are now being completed and have only been published in abstract form. Hence, conclusions derived regarding efficacy were tempered. RESULTS: Meropenem is active against a broad spectrum of gram-positive and -negative pathogens including beta-lactamase producers. Meropenem appears to be two- to fourfold less active than imipenem against gram-positive organisms. Meropenem is two- to fivefold more active against enterobacteriaceae. The two compounds appear to be equally active against Pseudomonas aeruginosa. Pharmacokinetic disposition is also similar for imipenem and meropenem. Meropenem may exhibit greater tissue penetration. Meropenem is not labile to renal hydrolysis and can be administered without a competitive antagonist of dihydropeptidase, such as cilastatin. In clinical trials, meropenem appears to be as safe and effective as imipenem/cilastatin or ceftazidime in the treatment of infections involving soft tissue, urinary tract, upper respiratory tract, abdominal processes, and febrile neutropenic episodes. CONCLUSIONS: Meropenem is comparable to imipenem in terms of in vitro susceptibility pattern and pharmacokinetic disposition. Overall, meropenem seems to offer promise as the second of the carbapenem class of antibiotics. Clinical data are preliminary, and further data are needed.

Increase in serum digoxin concentrations after indomethacin therapy in a full-term neonate.

Digoxin was administered to an 18-day-old infant who showed evidence of cardiac failure. When a Doppler echogram revealed a patent ductus, indomethacin was administered for medical management. Therapeutic digoxin doses then resulted in toxic serum concentrations of 8.2 ng/ml. Serum creatinine rose accordingly. Although this patient did not manifest signs of digoxin toxicity, practitioners should be alerted to the potential complications of these commonly used agents.

Effect of pharmacist participation on a medical team on costs, charges, and length of stay.

The financial impact of pharmacist participation on a medical team in a tertiary-care teaching hospital was studied prospectively. Two medical teams, one with and one without a pharmacist, operated simultaneously for 11 months. Physicians and a pharmacist on the teams rotated monthly during the first five months of the study. Subsequently, the hospital administrator, who was unaware that the controlled study was under way, permanently assigned an attending physician to the team that did ot have a pharmacist. After patients' discharge, pharmacy costs, pharmacy charges, hospital charges, and length of stay (LOS) were compared for the two teams. Data analysis was separated into four phases: phase 1, during which attending physicians rotated monthly; phase 2, with a permanent attending physician; phase 3, which encompassed the entire 11 months; and phase 4, which encompassed the 11-month period but omitted patients whose LOS exceeded 30 days. Data were analyzed for a total of 619 patients on the two teams. In phase 1, the team with a pharmacist had significantly lower per-patient pharmacy costs, pharmacy charges, hospital charges, and LOS. In phase 2, no significant differences were found between the teams. In phase 3, the only significant difference was that the team with a pharmacist had lower pharmacy costs and pharmacy charges. In phase 4, the team that included a pharmacist had significantly lower pharmacy costs ($105 difference), pharmacy charges ($368 difference), hospital charges ($2065 difference), and LOS (1.3-day difference). Participation of pharmacists on the medical team can significantly reduce pharmacy costs and charges, hospital charges, and LOS.