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Biomedical subjects

P D Walson

Publications and source records attributed to P D Walson.

At least 19 recordsLinked to original sources
PubMed1998

Therapeutic drug monitoring in special populations.

Therapeutic drug monitoring (TDM) is commonly used to maintain "therapeutic" drug concentrations. Even in compliant patients, with "average" drug kinetics, TDM is useful to identify the causes of unwanted or unexpected responses, prevent unnecessary diagnostic testing, improve clinical outcomes, and even save lives. TDM has greatest promise in certain special populations who are: (a) prone to under- or overrespond to usual dosing regimens, (b) least able to tolerate, recognize, or communicate drug effects, or who are (c) intentionally or accidentally misdosed. TDM is especially useful in patients at the extremes of age, in adolescents, and in patients who are either taking multiple drugs or expressing unusual pharmacokinetics as a result of physiological, environmental, or genetic causes. Less-well-appreciated uses of TDM include prevention of dangerous underdosing of patients, investigation of adverse drug reactions, and identification of serious medication errors, even for a number of drugs that are not traditionally monitored. TDM can be useful for some drugs in any patient and for most drugs in some special populations.

Age Factors↗
PubMed1997

Population pharmacokinetics of felbamate in children.

Information about the pharmacokinetics of felbamate in children is limited. Even though it is claimed that monitoring of felbamate concentrations is unnecessary, many neurologists have requested therapeutic drug monitoring (TDM) for various reasons. This study used the NONMEM program to describe the pharmacokinetics and the influence of other anticonvulsants on the pharmacokinetics of felbamate. Felbamate, carbamazepine (CBZ), phenytoin (PHY), valproate (VPA), and barbiturate serum levels were obtained by our TDM service as requested by the clinician. The clearance and volume of distribution of felbamate were 41.1 ml/h/kg and 908 ml/kg, respectively. CBZ and PHY increased the clearance 49 and 40% while VPA decreased it 21%. Barbiturate had no significant effect. Clearance also decreased with age.

Adolescent↗
PubMed1996

Serum lidocaine concentrations after subcutaneous administration in patients undergoing cardiac catheterization in a pediatric institution.

OBJECTIVE: We wished to determine serum lidocaine concentrations after subcutaneous injection during cardiac catheterization. METHOD: Serum lidocaine concentrations were measured in 50 patients during catheterization. RESULTS: Serum concentration was linearly related to dose per kilogram of body weight. Lidocaine concentrations were therapeutic in 38% of patients. CONCLUSION: Lidocaine dose must be considered when the drug is used for local anesthesia in children.

Anesthetics, Local↗
PubMed1996

Clonazepam disposition in pediatric patients.

Plasma clonazepam (CZP) and its metabolite [7-aminoclonazepam (7ACZP) and 7-acetamidoclonazepam (7AACZP)] concentrations were measured during a single dosing interval in 10 pediatric epilepsy patients (2-18 years, 11-102 kg) who had been receiving CZP therapeutically from 2 weeks to 4 years. These concentrations were used to determine CZP and metabolite pharmacokinetics. With controlled dosing and postdose sample collection times, large variations were observed in calculated CZP nitroreduction rates [clearance (CL/F) ranged from 7 to 64 ml/h/kg] as well as 7ACZP acetylation rates (CL/F from 10 to 85 ml/h/kg). No 7AACZP (i.e., < 5 ng/ml) was detected by the methods used. Acetylation rates are known to be under genetic control. Further studies are needed to determine whether nitroreduction rates are also under genetic control and whether differences in either of these metabolic rates can explain intraindividual differences in clinical responses observed in CZP-treated patients.

Acetylation↗
PubMed1994

Comparison of the pharmacokinetics of naproxen tablets and suspension in children.

Twenty-three children, aged 8 to 14 years, with postoperative pain, were randomly assigned to receive a fixed 250-mg dose (4.66-7.58 mg/kg) of naproxen as either a liquid suspension or tablet. After an overnight fast, the serum concentrations were measured before and at 0.5, 1, 2, 3, 4, 8, 12, 18, and 24 hours after administration of naproxen. The concentration versus time data were best fit to a one-compartment open model. The area under the concentration versus time curve, apparent volume of distribution (VDss/F), and elimination parameters (CL/F, Ke, elimination half-life) were similar in children who received suspension or tablets. Although the apparent maximum peak plasma concentration (Cmax) was greater in children who received tablets compared with those who received the suspension, Cmax/area under the curve (AUC), apparent time to maximum peak concentration (tmax), Ka, and estimated time to 10%, 50%, and 90% absorption (T10, T50, T90) were not different. The dose range was relatively narrow; hence, direct relationships between dose and elimination parameters, VDss/F, apparent tmax, Ka, T10, T50 or T90 were not observed. Neither VDss/F or CL/F were age related over the relatively narrow range of ages that were studied. Elimination of naproxen in our patients was more rapid than has previously been reported in children or adults, however. From a practical standpoint, naproxen tablets and suspension seem to be bioequivalent in fasting children ages 8 to 14 years.

Administration, Oral↗
PubMed1994

Anticonvulsant tolerance to clonazepam in amygdala kindled rats: clonazepam concentrations and benzodiazepine receptor binding.

The relationship between anticonvulsant tolerance to clonazepam and benzodiazepine receptor changes was studied in amygdala kindled rats. Fully kindled rats were given 1 mg/kg clonazepam (clonazepam treated) or vehicle (kindled control) orally three times per day for 4 weeks. During chronic treatment, amygdala stimulation was given twice per week, 30 min after a single protective dose of clonazepam (0.5 mg/kg, i.p.) was injected to both groups of rats. As measured by seizure stage, clonazepam treated rats showed a greater degree of tolerance than kindled control rats; contingent tolerance to the anticonvulsant effects of clonazepam developed in kindled control rats, while clonazepam treated rats shows contingent plus pharmacologic tolerance. There were no significant differences between clonazepam treated and kindled control rats in "peak" plasma clonazepam concentrations 40 min after clonazepam injections. Benzodiazepine receptor assays showed no significant difference in maximal binding capacity (Bmax), dissociation constant (Kd) or gamma-aminobutyric acid (100 microM) enhancement of benzodiazepine receptor binding between clonazepam treated and kindled control rats. These data suggest that pharmacologic tolerance to anticonvulsant action of clonazepam is not related to either plasma clonazepam concentrations or benzodiazepine receptor changes.

Amygdala↗
PubMed1994

Phenytoin age-dose-concentration relationship in children.

A list (n = 423) of phenytoin steady-state concentrations from children taking phenytoin alone or in combination with other drugs (n = 308) was obtained from our therapeutic drug monitoring database (1984-1990). Only 43% of concentrations were within the commonly accepted "therapeutic" or "reference" range (10-20 mg/L). Age-dose-concentration relationships showed that while occasional concentrations were above 20 mg/L, many patients receiving commonly recommended pediatric phenytoin doses (4-8 mg/kg/day) achieved concentrations below the reference range, especially children under 3 years of age. Michaelis-Menten pharmacokinetic parameters, maximal elimination rate (Vmax) and Michaelis constant (Km), were evaluated for patients with at least two steady-state concentrations measured for two or more different daily doses. Comedication with other drugs had no effect on either Vmax or Km for phenytoin. Vmax appeared to decrease significantly with age, but there was no age relationship for Km.

Adolescent↗
PubMed1993

Antiepileptic effect of antiepilepsirine in pentylenetetrazol and amygdala kindled rats.

Antiepilepsirine (AES) is a new antiepileptic drug developed in China. Anticonvulsant effects of AES were studied in both pentylenetetrazol (PTZ, n = 20) and amygdala kindled (n = 10) rats. AES was given once per day by oral gavage for 4 weeks. On days 7, 14, 21 and 28, all rats were tested 2 h after daily AES administration: PTZ and amygdala kindled rats were given a PTZ injection (30 mg/kg, i.p.) or amygdala stimulation (400 microA, 1 s), respectively. Behavior was observed, and seizures were graded. AES (300 or 500 mg/kg) produced sustained, dose dependent, protective effects against PTZ induced seizures in PTZ kindled rats, while AES (500 mg/kg) had no effects in amygdala kindled rats.

Amygdala↗
PubMed1993

Intermittent clonazepam treatment prevents anticonvulsant tolerance in mice.

The influence of intermittent benzodiazepine treatment on anticonvulsant tolerance was studied by comparing mice treated either daily or on alternate days with clonazepam, 0.25 mg/kg, i.p., administered twice a day. Tolerance was assessed by the ability of clonazepam to prevent pentylenetetrazol (PTZ) induced clonic convulsions. In mice treated daily with clonazepam, significant tolerance was evident after 5 days of treatment but did not increase further after 10 or 20 days of treatment. However, mice treated with clonazepam only on alternate days for 10 or 20 days showed no tolerance. Our data indicate that intermittent treatment may prevent development of tolerance to the anticonvulsant action of benzodiazepines.

Animals↗
PubMed1993

Audit of theophylline plasma level monitoring in a pediatric hospital.

Theophylline assays performed in a children's hospital were audited, focusing particularly on distribution of plasma concentration values, interpretation of the assay result, appropriateness of the advice conveyed to the physician, and the response to this advice. Assays performed by a multidisciplinary therapeutic drug monitoring (TDM) service during a 1-month period in 1988 and again in 1992 were chosen for review. Theophylline concentration in plasma was quantified by fluorescence polarization immunoassay. Medical technologists interpreted results and made specific recommendations concerning dose changes and/or need for follow-up assays on 48.5 (1988 survey) and 37.9% (1992 survey) of results. Review of these recommendations revealed that only approximately 1% could have been improved or were incorrect. Physician compliance with dose change recommendations was similar in both surveys (chi 2 = 0.16, p = 0.7), with recommendations being followed on 75.9 (1988) and 73.3% (1992) of occasions. Compliance with recommendations for ordering additional samples at specific times also was similar between the two surveys (chi 2 = 2.06, p = 0.15), with recommendations being followed on 75 (1988) and 87.2% (1992) of occasions. Overall, combining the data for both surveys, (a) significantly more out-patients than in-patients (69.2 versus 27.8%, respectively) were subtherapeutic, (b) significantly fewer out-patients than in-patients (27.6 versus 70.2%, respectively) were within the therapeutic range (chi 2 = 33.7, p < 0.001), but (c) numbers (2-4%) of potentially toxic results within the two groups were similar.

Asthma↗
PubMed1993

Principles of drug prescribing in infants and children. A practical guide.

Paediatric prescribing is much more complicated than prescribing for adults. The specific and general aspects of paediatric patients, the limitations of commercially available dosage formulations, the vagaries of administering medicines, the general inadequacy of clinical pharmacology training, and the dearth of information about drug use in children all add to the difficulties facing the practitioner who treats infants and children. For these reasons practitioners should prescribe judiciously, select carefully the safest dosage regimen available, and educate their patients, caregivers and staff about their choices and expected positive and negative effects. Practitioners should also have available and use written, electronic, as well as human sources of expert advice. They should write all prescriptions legibly and carefully, document their therapeutic decisions and plans, and carefully monitor their patients' responses to therapy. Careful attention to the principles of clinical pharmacology can do much to improve the efficacy of paediatric prescribing and decrease its costs and risks.

Child, Preschool↗
PubMed1993

[Development of pentylenetetrazol kindling model].

An ideal animal model of chemical kindling mimicking human epilepsy was developed in 28 day-old rats. Rats were given pentylenetetrazol (PTZ) 30 mg/kg, ip, once per day for 28 consecutive days; after stopping treatment for one week, the rats were retreated using the same dose of PTZ until reaching the kindled criterion. The kindled rate was 74%. The behavioral seizure and EEG discharges were synchronized. All kindled rats still kept their high seizure state after the experiments.

Animals↗
PubMed1993

Levodopa/carbidopa for childhood amblyopia.

PURPOSE: To evaluate the efficacy and tolerance of two low doses of levodopa/carbidopa (25/6.25 mg, 50/12.5 mg) and placebo (Tums) in 20 children with amblyopia between the ages of 4 and 14 years. METHODS: A double-masked placebo-controlled randomized 8-hour study was performed during which subjects received one of two doses of levodopa/carbidopa or placebo, combined with occlusion of the dominant eye. Visual acuity was measured at baseline and at 1 and 5 hours after capsule ingestion. Tolerance was assessed by questionnaire and physical examination. RESULTS: Visual acuity significantly improved by one line, from an overall average of 20/121 to 20/96, in the amblyopic eyes of both groups that received levodopa/carbidopa. Visual acuity did not significantly change in the placebo group. Tolerance was similar among all three groups. CONCLUSION: Average dose levels of 0.95/0.24 mg/kg and 1.94/0.49 mg/kg of levodopa/carbidopa were found to be well tolerated and efficacious at temporarily improving visual acuity in amblyopic eyes of children.

Adolescent↗
PubMed1992

Comparison of multidose ibuprofen and acetaminophen therapy in febrile children.

OBJECTIVE: To determine whether febrile children receiving 2.5-, 5-, or 10-mg/kg ibuprofen therapy via a liquid or 15-mg/kg acetaminophen therapy via an elixir every 6 hours for 24 to 48 hours show equivalent fever reduction or suffer adverse effects of the drug administered. DESIGN: Randomized, double-blind, multidose, parallel-group, variable-duration (24 to 48 hours) clinical trial. SETTING: The academically affiliated Children's Hospital in Columbus, Ohio. PARTICIPANTS: 64 febrile (defined as oral or rectal temperature of 39 degrees C to 40.5 degrees C) but otherwise healthy children aged 6 months to 11 years 7 months randomly assigned to one of the four drug regimens. INTERVENTIONS: Treatment with either ibuprofen or acetaminophen as described above. Administration of antibiotics or intravenous fluids was allowed only after at least 24 hours of treatment with the assigned drug. MEASUREMENTS/MAIN RESULTS: In 61 of the 64 evaluable patients, treatments were effective and well tolerated during the entire study. While the rates of temperature reduction and maximal reduction of fever after administration of the initial dose were equal for patients receiving 10-mg/kg ibuprofen therapy and 15-mg/kg acetaminophen therapy, and both regimens were more effective than smaller doses of ibuprofen in reducing fever, after the second dose (and continuing to the end of the study) there were no statistically significant differences in temperature response among the treatment groups. Six children were withdrawn from the study, two because of dosing errors, three because of hypothermia (temperature of less than 35.6 degrees C; all three patients were in the acetaminophen group), and one because of gastrointestinal distress (this child was in the group receiving 2.5-mg/kg ibuprofen therapy). No other significant symptoms or adverse laboratory or physical findings were noted. While further confirmatory studies are needed, ibuprofen liquid (10 mg/kg) and acetaminophen elixir (15 mg/kg) administered every 6 hours for 24 to 48 hours appeared to be most effective in reducing fever. These two regimens were equally effective and equally tolerated in febrile children. Lower ibuprofen doses (2.5 and 5 mg/kg) were less effective than acetaminophen and 10-mg/kg ibuprofen therapy after the initial dose but were at least equally effective as these two higher-dose regimens thereafter.

Acetaminophen↗