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Biomedical subjects

P Walson

Publications and source records attributed to P Walson.

12 recordsLinked to original sources
PubMed2001

The pharmacokinetics of enalapril in children and infants with hypertension.

Forty children with hypertension between the age of 2 months and 15 years received 0.07 to 0.14 mg/kg of enalapril as a single daily dose. Enalapril was administered orally as a novel extemporaneous suspension in children younger than 6 years of age and as tablets in older children. First-dose and steady-state pharmacokinetics were estimated in children ages 1 to 24 months, 25 months to < 6 years, 6 to < 12 years, and 12 to < 16 years. Maximum serum concentrations for enalapril occurred approximately 1 hour after administration. Serum concentrations of enalaprilat, the active metabolite of enalapril, peaked between 4 and 6 hours after the first dose and 3 and 4 hours after multiple doses. The area under the concentration versus time curve (AUC), adjusted for body surface area, did not differ between age groups. Based on comparison of first-dose and steady-state AUCs, the accumulation of enalaprilat in children ranged from 1.13- to 1.45-fold. For children ages 2 to 15 years, mean urinary recovery of total enalaprilat ranged from 58.3% in children ages 6 to < 12 years to 71.4% in children ages 12 to < 16 years. Urinary recovery for children ages 2 to < 6 years was 66.8%. The mean percentage conversion of enalapril to enalaprilat ranged from 64.7% for children ages 1 to 24 months to 74.6% for children ages 6 to < 12 years. The median effective half-life for accumulation ranged from 14.6 hours in children ages 12 to < 16 years to 16.3 hours in children ages 6 to < 12 years. There were two serious adverse events, neither of which was attributed to enalapril or resulted in discontinuation of the study drug. The extemporaneous suspension used in this study was tolerated well. The pharmacokinetics of enalapril and enalaprilat in hypertensive children ages 2 months to 15 years with normal renal function appears to be similar to that previously observed in healthy adults.

Adolescent↗
PubMed2000

Research Units on Pediatric Psychopharmacology (RUPP) Autism Network. Background and rationale for an initial controlled study of risperidone.

This article has reviewed the background and rationale for the choice of risperidone as the first drug to be studied by the RUPP Autism Network. Risperidone has potent effects on 5-HT and DA neuronal systems, both of which have been implicated in the pathophysiology of autism. Unlike the typical antipsychotics, haloperidol and pimozide, which have been shown to be effective for reducing many of the maladaptive behaviors associated with autism, risperidone's 5-HT2A/DA D2 ratio of receptor blockade appears to produce a lower risk of acute and chronic extrapyramidal side effects, as well as enhanced efficacy for the "negative" symptoms of autism. Indirect clinical and preclinical evidence supports the use of risperidone to treat impaired social behavior, interfering repetitive phenomena, and aggression, targets of pharmacotherapy for many patients with autism. Numerous published open-label trials in children and adolescents with autism and related PDDs and one double-blind, placebo-controlled study in adults suggest that risperidone has promise for the treatment of children and adolescents with autism. Because most of these studies have been short-term, open-label trials in small samples, however, a large-scale controlled study of risperidone in children and adolescents with autism is needed to confirm these results. Finally, because it is likely that children who demonstrate short-term benefit from risperidone will remain on the medication indefinitely, the longer-term effectiveness and safety of risperidone in this population also needs to be determined. The design of this study and the assessments used are described separately.

Adolescent↗
PubMed1993

Safety of vancomycin with or without gentamicin in neonates.

Short- and long-term side effects of vancomycin, or the combination of vancomycin and gentamicin, were retrospectively evaluated for 65 treatment courses in 47 premature infants who were exposed to high vancomycin serum concentrations. Thirty-five treatment courses involved treatment with the combination; 30 courses involved treatment with vancomycin alone. No immediate side effects were noted. Nephrotoxicity, defined as an increase in serum creatinine 0.5 mg/dl or more above baseline, was found in only 1 patient receiving vancomycin as the only antibiotic; that patient had pre-existing renal dysfunction. Three treatment courses involving the vancomycin-gentamicin combination resulted in nephrotoxicity; renal function returned to normal by 14 days after treatment. Thrombocytopenia was noted in 5 patients, but none exhibited clinical bleeding. Low platelet counts persisted throughout treatment, but by two weeks after treatment, this was resolved. In conclusion, the use of vancomycin or the combination of vancomycin and gentamicin in seriously ill premature infants is usually safe. The adverse effects noted were reversible, and monitoring creatinine and platelet counts during treatment is recommended.

Drug Monitoring↗
PubMed1992

Strychnine poisoning in an adolescent.

One half hour following the ingestion of a possibly tainted antibiotic capsule, a 14 year-old female experienced acute onset of stiffness and weakness in her lower extremities. She subsequently survived despite the development of convulsions, severe lactic acidosis (pH 6.86), hyperthermia (Temp 40.5 degrees C) and rhabdomyolysis. Toxicology testing confirmed the presence of strychnine in blood, gastric aspirate, and urine. Her course, history and outcome are presented and the pharmacokinetics, the mechanism of action, signs and symptoms and treatment of strychnine poisoning are reviewed.

Adolescent↗
PubMed1987

Carbamazepine plasma concentration. Relationship to cognitive impairment.

Neuropsychological function was assessed before and after carbamazepine monotherapy in children with newly diagnosed complex partial epilepsy. Simultaneous video-electroencephalographic monitoring examined the influence of subclinical abnormal electrical discharges on performance. Total and unbound plasma carbamazepine concentrations were examined in relation to changes in performance at low (carbamazepine level, less than or equal to 32 mumol/L [less than or equal to 7.5 mg/L]) and moderate (carbamazepine level, greater than 34 mumol/L [greater than 8.0 mg/L]) drug levels. The data suggest a mild beneficial effect of carbamazepine on speeded eye-hand coordination and, at low drug levels, more rapid processing of items in memory. Efficiency of learning new information and memory-scanning rate displayed a concentration-dependent relationship with carbamazepine level, with poor performance significantly associated with higher carbamazepine plasma concentrations. Carbamazepine free levels were equivalent to total levels in predicting cognitive side effects.

Carbamazepine↗
PubMed1983

Kinetics of clonazepam in relation to electroencephalographic and clinical effects.

The aim of this study was to see if the immediate EEG and clinical response to an intravenous dose of clonazepam was predictive for the effect of oral clonazepam maintenance therapy. Four children with petit mal epilepsy were given clonazepam intravenously during continuous EEG recording. Clonazepam plasma concentrations were determined repeatedly with a high performance liquid chromatographic method using a reversed phase system. The day after the intravenous dose the patients were given oral therapy with clonazepam. Repeated long-term EEG recordings were made and plasma concentrations of clonazepam were determined. There was no clinically satisfactory effect of clonazepam during oral maintenance treatment in three of the children who responded well to the intravenous dose of clonazepam. Thus, the immediate response to intravenous clonazepam was not a good predictor of the long-term effects in our patients.

Adolescent↗
PubMed1982

Regional epidural analgesia: kinetics of pethidine.

Low intrathecal doses of opiates produce dose-dependent long-wasting elevation of the pain threshold in rats. The effect is postulated to be mediated by a direct action on the substantia gelatinosa of the spinal cord. Eight uncontrolled and two controlled studies in man showed a long duration of analgesia for most patients in the postoperative period. The duration of effect differs widely within and between studies. Using a double-blind design, we compared the relative efficacy of epidural and parenteral pethidine to control postoperative pain after total hip replacement. Preliminary pharmacokinetic data from six patients show that epidural doses of 20 or 60 mg pethidine give a similar pattern of absorption and elimination in plasma as 2 mg pethidine/kg body weight intramuscularly. The terminal elimination half-lives of pethidine in plasma are 5-7 h for all routes of administration. The possibility cannot be excluded that the analgesic effect of epidural pethidine is partly systemically mediated.

Anesthesia, Conduction↗
PubMed1980

Effect of dose on phenytoin absorption.

To determine the effect of dose on phenytoin bioavailability, a single intravenous 15-mg/kg dose, single oral doses of 400, 800, and 1,600 mg, and 1,600 mg in divided doses (400 mg every 3 hr) were given to six healthy male subjects. Values of Vmax (maximum elimination rate) and Km (serum concentration at which rate of elimination is one half the maximum rate) from the intravenous dose were used to determine the extent of absorption. Although no statistically significant difference in extent of phenytoin absorption was detected, the time to reach maximum phenytoin serum concentrations increased from 8.4 hr for the 400-mg dose and 13.2 hr for the 800-mg dose to 31.5 hr for the 1,600-mg dose. After the 400, 800, and 1,600-mg doses and 1,600-mg divided doses, the serum concentration peaks were 3,9, 5.7, 10.7, and 15.3 mg/l. It is suggested that the prolonged, but complete, absorption of large phenytoin doses is due to slow dissolution and continued absorption from the colon. Due to prolonged absorption of phenytoin, it may be necessary to use larger oral than intravenous loading doses to achieve the same maximum phenytoin serum concentrations.

Administration, Oral↗
PubMedDate not supplied

Levodopa and childhood amblyopia.

A pilot study was undertaken to address the tolerance and efficacy of levodopa/carbidopa treatment for amblyopia in older amblyopic children who failed to respond to conventional occlusion therapy. Five amblyopic children, between the ages of 7 and 12 years, and two normal adults were given between 100 mg/25 mg and 400 mg/100 mg of levodopa/carbidopa, respectively, depending on body weight. A symptoms questionnaire was completed, with temperature, respiration, heart rate, and blood pressure taken periodically to assess tolerance. Blood samples were taken, via a heparin well, to assess the pharmacokinetics of levodopa, dopamine, noradrenaline, and DOPAC. Snellen visual acuity, contrast sensitivity, stereo acuity, and pattern VERs were measured periodically to assess efficacy. The results revealed a high prevalence of side effects including emesis and nausea (four of seven subjects). Pharmacokinetics revealed that maximum serum levels of levodopa occurred 30 minutes to 1 hour after drug ingestion and decreased by 50% after 2 to 4 hours. One hour after drug ingestion, Snellen visual acuity temporarily improved from an average of 20/159 to 20/83 in the amblyopic eyes. Contrast sensitivity and pattern VERs (10-minute checks) temporarily improved in both dominant and amblyopic eyes, whereas visual function remained stable in normal eyes. The improvements in visual function started to decrease 5 hours after drug ingestion. The results are discussed in the context of developing a therapeutic trial of levodopa/carbidopa for childhood amblyopia.

Adult↗