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Biomedical subjects

P Gal

Publications and source records attributed to P Gal.

At least 55 records · Page 3Linked to original sources
PubMed1989

Carbamazepine clearance in hemodialysis and hemoperfusion.

A 47-year-old woman with endstage renal disease and dialysis-induced encephalopathy was being treated with carbamazepine for myoclonus. Her carbamazepine serum concentration appeared to be therapeutic at 5.1 micrograms/ml. She experienced a seizure while on hemodialysis/hemoperfusion that was possibly related to the removal of carbamazepine during dialysis. The elimination of carbamazepine on a dialysis day was compared with elimination on a nondialysis day. The half-life and apparent clearance were the same for each day, indicating that hemodialysis/hemoperfusion had little effect on the overall removal of carbamazepine from the body. The possible reasons for this lack of effect are discussed.

Carbamazepine↗
PubMed1989

Rapid sequential phenobarbital treatment of neonatal seizures.

The optimal serum concentration of phenobarbital in newborns and its safety at high doses are not well established. The dose response relationship of rapid sequential phenobarbital loading in the newborn was examined and the efficacy of high-dose monotherapy was compared with the addition of a second anticonvulsant for persistent seizure activity. A single loading dose of phenobarbital 15 to 20 mg/kg was initially administered to 120 newborns. Nonresponders received sequential bolus doses of 5 to 10 mg/kg until seizures ceased or a serum concentration of 40 micrograms/mL was obtained. Infants with refractory seizures received additional phenobarbital to a maximum serum concentration of 100 micrograms/mL. The seizures of 48 babies (40%) were controlled after initial loading and 37 of the remaining 72 subjects (51%) responded at serum concentrations of as great as 40 micrograms/mL. The seizures of only seven subjects were controlled at greater concentrations. A second anticonvulsant controlled seizures in 13 of the 28 subjects (46%) whose seizures were refractory to phenobarbital. A gestational age of less than 32 weeks was associated with a significantly better response to phenobarbital. Serum phenobarbital concentrations greater than 50 micrograms/mL produced only occasional feeding difficulty and sedation. It was concluded that sequentially administered IV phenobarbital controls seizures in both term and preterm newborns (77%). This therapeutic effect is dose dependent but plateaus at a serum concentration of 40 micrograms/mL. At greater serum concentrations, unresponsive patients should receive a second antiepileptic agent.

Dose-Response Relationship, Drug↗
PubMed1988

The effect of total parenteral nutrition-induced cholestasis on theophylline clearance in neonates.

The effect of total parenteral nutrition (TPN) induced cholestasis on theophylline clearance was examined in premature neonates. Thirty-six neonates receiving TPN and theophylline concurrently were reviewed. Aminophylline was administered according to a standard protocol of 6 mg/kg loading dose, followed by a maintenance dose of 2.5-5 mg/kg every 12 h. Of the 36 neonates reviewed, 18 developed cholestasis (direct bilirubin greater than or equal to 1 mg/100 ml and direct bilirubin greater than or equal to 60% of total bilirubin). The remaining 18 did not develop cholestasis. The two groups were closely matched for gestational age, 5-min apgar score, and sex. The neonates with cholestasis had a mean maximum direct bilirubin of 5.19 mg/100 ml (range 1-13.8 mg/100 ml) as compared to the patients without cholestasis who had a mean maximum direct bilirubin of 0.54 mg/100 ml (range 0.3-0.8 mg/100 ml). Steady-state theophylline clearance was determined at least once a week for at least 4 separate weeks. The study lasted a minimum of 8 weeks, and if more than one theophylline clearance was determined in any given week, the mean of these clearances was used. Both groups demonstrated a significant increase in mean theophylline clearance over time (from 16.09 and 18.60 ml/h/kg to 28.65 and 24.73 ml/h/kg for the cholestatic and noncholestatic groups, respectively). The mean slope, an indicator of the average rate of change of theophylline clearance, was 1.4 for the noncholestatic group and 2.5 for the cholestatic group, indicating that the theophylline clearance for neonates with cholestasis was not significantly different from that for neonates with normal liver function (p = 0.61) over time.

Bilirubin↗
PubMed1988

Therapeutic drug monitoring in neonates: problems and issues.

Therapeutic drug monitoring has been applied in several patient populations to promote safer, more effective use of drugs. The development of therapeutic ranges allows clinicians to aim for a plasma drug concentration that is usually safe and effective, and calculation of specific pharmacokinetic parameters allows selection of doses that will achieve the desired plasma concentration. This concept certainly holds true in the intensive care nursery; however, the intensity of monitoring in this setting provides opportunities for far broader applications of the information obtained from drug concentration monitoring. This review provides an overview of the complexity of and potential applications for therapeutic drug monitoring in neonates based on literature and clinical experience.

Humans↗
PubMed1988

Valproic acid efficacy, toxicity, and pharmacokinetics in neonates with intractable seizures.

Six neonates with prolonged, intractable seizures were treated with valproic acid (VPA). Each patient had received maximum doses of phenobarbital (greater than 40 micrograms/ml), and five patients received at least two additional anticonvulsants, without success. Seizure activity was controlled in five of six (83%) cases. In four cases, all other anticonvulsants could be withdrawn, and seizures were controlled on VPA monotherapy. VPA was discontinued in three patients because of VPA-induced hyperammonemia. VPA pharmacokinetic measurements were as follows: for total VPA, volume of distribution (V) = 0.40 l/kg (range, 0.36 to 0.47 l/kg), serum clearance (Cl) = 14.4 ml/h/kg (5.5 to 18.2 ml/h/kg), half-life (T1/2) = 26.4 hours (8.6 to 48.5); for unbound VPA, V = 2.02 l/kg (1.14 to 2.44 l/kg), Cl = 108.9 ml/h/kg (42.0 to 252.0 ml/h/kg). T1/2 = 17.6 hours (6.7 to 34.2). VPA free fraction ranged from 11.3 to 31.6% (mean, 19.2%).

Absorption↗
PubMed1987

The effect of oral cimetidine on total and unbound serum lidocaine concentrations in patients with suspected myocardial infarction.

In this study, we prospectively evaluated the effect of oral cimetidine on serum lidocaine concentrations in 6 patients with suspected myocardial infarction. Compared to baseline lidocaine levels, total lidocaine concentrations increased by 8.2 +/- 7.8% at 6 hours, 16.4 +/- 9.0% at 12 hours and 27.9 +/- 9.4% at 24 hours after two doses of oral cimetidine. Unbound lidocaine concentrations increased by 14.3 +/- 4.1% at 6 hours, and 18.3 +/- 10.3% at 24 hours after cimetidine. In patients with myocardial infarction (3), total lidocaine concentrations increased by 24.2 +/- 10.4%, whereas unbound lidocaine increased by 8.9 +/- 10.2% at 24 hours. Therefore, increases in total lidocaine concentrations after cimetidine administration were considerably less than those previously reported and empiric dosage reductions of lidocaine in patients receiving cimetidine may not be appropriate.

Administration, Oral↗
PubMed1987

Peritoneal transport of cefonicid.

The pharmacokinetic characteristics of cefonicid, a highly protein-bound expanded-spectrum cephalosporin, were examined in six noninfected, clinically stable patients undergoing continuous ambulatory peritoneal dialysis. After a 1.0-g intravenous dose of cefonicid, the mean concentrations in serum were 105 +/- 25 and 35.6 +/- 14.4 micrograms/ml at 3 and 72 h, respectively. Despite a prolonged half-life in serum of 49.7 +/- 18 h, the penetration into peritoneal fluid was low. The average concentration in dialysate over the 72-h study period was 2.7 micrograms/ml. The serum clearance was 2.6 +/- 1.0 ml/min, and the distribution volume was 0.14 +/- 0.02 liter/kg. Dosage recommendations and clinical considerations for cefonicid use in continuous ambulatory peritoneal dialysis patients are discussed.

Cefamandole↗
PubMed1987

Heparin dosage adjustment in patients with deep-vein thrombosis using heparin concentrations rather than activated partial thromboplastin time.

In patients with deep-vein thrombosis, heparin dosage adjustment based on measurement of heparin concentrations in whole blood was compared with conventional dosage adjustment based solely on activated partial thromboplastin time (APTT) measurement. Initially, all patients were given i.v. bolus doses of heparin sodium 70 units/kg followed by continuous infusion of 16 units/kg/hr. Seventeen patients (group 1) had their initial heparin dosages adjusted according to the results of the APTT value four hours after the start of heparin therapy; subsequent adjustments were made to maintain APTT values within the therapeutic range of 1.5 to 2.5 times the patient's baseline control. Fifteen patients (group 2) had heparin dosage adjusted four hours after the start of heparin infusion, based on apparent heparin clearance using the two-point method of Chiou et al., to maintain whole-blood heparin concentrations of 0.3 to 0.6 units/mL. APTT values less than 1.5 times control occurred in about 12% of group 1 patients at 8, 12, and 24 hours and in 11 of 17 (65%) for at least one value during the study. In group 2 patients, no APTT values were less than 1.5 times control. The patients in group 2 had faster symptomatic improvement and shorter hospital stays. Heparin dosing based on measurement of whole-blood heparin concentrations and application of a practical two-point pharmacokinetic model was superior to dosing based on APTT values.

Adult↗
PubMed1986

Physicians' opinions of the accuracy, accessibility, and frequency of use of ten sources of new drug information.

We surveyed internists, surgeons, and general practitioners in a six-county area of North Carolina to determine how accurate and accessible they believed ten sources of new drug information to be and how frequently they used each of the sources. Evaluable questionnaires were returned by 119 of the 336 physicians. The majority indicated that all sources were accessible. Commercial sources were thought to be less accurate than noncommercial sources, but were used more frequently (P less than .0002), especially by physicians who had practiced more than 15 years (P less than .02). Written sources were thought to be more accurate (P less than .0001) and were preferred over oral sources of new drug information (P less than .0004). Pharmacists and pharmacology textbooks were believed to be both accurate and accessible, but were relatively infrequently used.

Adult↗
PubMed1986

Factors influencing theophylline disposition in 179 newborns.

The pharmacokinetics of intravenous theophylline were prospectively studied in 179 premature babies. Interrelated variables were analyzed for their influence on theophylline serum clearance. Gestational age, gender, duration of treatment, body weight, and Apgar scores were not found to correlate significantly with theophylline clearance. Weak but statistically significant correlations were found between serum clearance and postnatal (p less than 0.005) and postconceptional age (p less than 0.01). No significant difference in mean serum clearance (Cls) values was found between small-for-gestational-age (SGA) patients (Cls = 17.9 +/- 5.3 ml/kg/h) and appropriate-for-gestational-age (AGA) patients (Cls = 18.8 +/- 5.8 ml/kg/h). Conversely, asphyxiated patients had significantly lower mean clearance values than nonasphyxiated patients (16.4 +/- 5.3 ml/kg/h vs. 20.2 +/- 5.4 ml/kg/h, respectively, p less than 0.001). Volume of distribution for theophylline (n = 147) was 0.77 +/- 0.17 L/kg; there was no significant difference in distribution volumes between asphyxiated and nonasphyxiated patients or between SGA and AGA patients. Step-wise multiple regression analysis revealed postnatal age as the most important determinant of theophylline clearance among the variables analyzed (p less than 0.01). Postconceptional age had a statistically significant association with theophylline clearance in the entire group (n = 179, p less than 0.05). Duration of treatment had a small and statistically borderline effect (p less than 0.10) on theophylline clearance among nonasphyxiated infants when age factors were considered. Analysis of covariance confirmed the statistical effects of both postnatal age and asphyxia on theophylline serum clearance.

Apgar Score↗
PubMed1986

Interference with oral theophylline absorption by continuous nasogastric feedings.

Continuous enteral feedings through a nasogastric tube is the preferred route of nutritional support for malnourished patients with inadequate spontaneous oral intake. However, in patients also receiving oral medications, the use of continuous nasogastric feedings may cause malabsorption of the drugs and consequently increase the risk of an inadequate clinical response. We report a case of an elderly patient with subtherapeutic theophylline serum concentrations and recurrent bronchospasm while receiving oral theophylline and continuous enteral feedings.

Food, Formulated↗
PubMed1986

Inadequacy of FDA dosing guidelines for theophylline use in neonates.

The efficacy of the FDA guidelines for theophylline dosing in newborns was evaluated retrospectively in 224 patients who had clearance data available. Mean projected post loading dose serum concentration was 4.1 +/- 1.0 mg/L in 160 patients. Mean projected steady-state concentration was 4.8 +/- 1.6 mg/L in 189 patients receiving intravenous aminophylline and 4.2 +/- 1.3 mg/L in 35 patients on oral therapy. Projected serum concentrations were subtherapeutic (less than 6.0 mg/L) in 181 of the 224 patients analyzed. There was a statistically significant difference in serum concentrations between asphyxiated and nonasphyxiated patients (p less than 0.001). There was no significant difference in mean projected serum concentrations between patients age 26-41 weeks (postconceptional age). This study suggests that the FDA dosing guidelines for theophylline in infants is inadequate and results in subtherapeutic (less than 6.0 mg/L) serum concentrations in the majority of newborns.

Humans↗