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Biomedical subjects

P Friel

Publications and source records attributed to P Friel.

18 recordsLinked to original sources
PubMed1995

Interaction of condom design and user techniques and condom acceptability.

In 1991, the source of public sector condom supplies in an African country changed from USAID to WHO. Following a complaint, the two types of condoms were sampled and compared. Laboratory tests indicated that the new-style condoms were of adequate quality, but a number of differences were noted between the two types. Complaints that the condoms were short and broke frequently could not be reconciled with measurements. Lubricant quantities on the WHO-supplied condoms were found to be lower than on the USAID condoms, but still within the range found on the commercial market. Also, the WHO condoms were marginally narrower and thicker. WHO asked the authors to conduct field interviews to seek reasons for the reported problems. These revealed that the relative dissatisfaction with the WHO condoms was largely confined to a group of sex workers in a follow-up programme conducted by two educators funded by a European agency. The instructions for use being given by the educators magnified the risk of incorrect application of the condom. Design changes to the WHO condoms (regarding lubricant, size and thickness) were subsequently made to minimise the chance of wrong use.

Africa↗
PubMed1990

Valproyl CoA: an active metabolite of valproate?

Valproic acid exhibits a time course of antiepileptic effects suggesting a major role for active metabolites. It is proposed that valproyl-CoA, a valproate metabolite previously identified in liver, may accumulate in brain as a result of normal fatty acid turnover processes. Valproyl CoA could contribute to valproate's antiepileptic activity by stimulating Na+, K+-ATPase activity when brain ATP concentration is low.

Acyl Coenzyme A↗
PubMed1989

Determination of enzyme or binding constants using generalized linear models, with particular reference to Michaelis-Menten models.

The estimation of Michaelis-Menten pharmacokinetic parameters in patients with epilepsy receiving phenytoin continues to be a vexing problem. The various approximate methods suggested in the literature have serious shortcomings, primarily due to the role of the error term in the statistical model. In this report we present an accurate statistical approach using the Generalized Linear Interactive Modeling (GLIM) computer package developed by the Numerical Algorithms Group, Oxford, U.K. There are several advantages to this model: a meaningful error term can be maintained by means of a link function, the model can incorporate within-subject and between-subject variables, and additional potential explanatory variables can be added to the model. The method is applied to predicting serum phenytoin levels of pregnant women monitored at monthly intervals during pregnancy and for two to five months after pregnancy. Michaelis-Menten parameters are estimated for each women and compared.

Adult↗
PubMed1989

Valproic acid disposition and protein binding in pregnancy.

Nine epileptic women were followed prospectively through pregnancy on a monthly basis. At each visit, total and free serum valproic acid levels and albumin levels were obtained. Assays were done by gas-liquid chromatography, and free drug was separated by ultrafiltration. Despite an upward dose adjustment in four patients, total valproic acid levels declined as pregnancy proceeded, but free levels did not. Plasma free fractions and clearances increased, but intrinsic clearances, which were adjusted for changes in body weight, remained unchanged.

Adult↗
PubMed1984

Effect of enteral tube feeding on serum phenytoin levels.

The primary purpose of the present study was to determine if altering the timing of phenytoin administration in relation to delivery of tube feedings increased serum phenytoin levels. Stopping tube feedings for two hours before and two hours after administration is a procedure that nurses could employ independently for better patient care. However, this adds an extra procedure to the nurse's already busy routine. It also requires the nurse to adjust either the tube feeding flow rate or bolus amount in order to deliver the same amount of calories per day. Based on this study, it appears that this intervention procedure is not effective for the patient and is time-consuming for the nurse. Instead, the focus for increasing phenytoin serum levels in patients receiving tube feedings should probably be on increasing the dosage.

Adult↗
PubMed1982

Development and evaluation of an inhibitor-releasing matrix for intrauterine devices.

Antifibrinolytic agents when released into the uterine cavity decrease menorrhagia associated with IUD use. Our objective was to develop a matrix that could be incorporated onto an IUD and release anti-fibrinolytic agents. The copolymer ethylene-vinyl acetate (EVA) was selected for detailed study because it has the advantage over other materials in that it can release large molecular weight substances for more than 100 days, and allows incorporation of large amounts of anti-fibrinolytic agents with different molecular weights. Two compounds, tranexamic acid (AMCA, MW=157) and Trasylol (Kunitz pancreatic trypsin inhibitor, (MW=6,500) were incorporated into the EVA matrix and their release rates measured. In vitro studies with AMCA showed that after the initial burst, a constant high release rate was obtained over a prolonged period of time. The in utero release rate of AMCA from the EVA matrix in rabbits was similar to that obtained in vitro. By contrast, the release rate of Trasylol decreased to low levels during incubation in vitro. The release rate of Trasylol in utero however, appeared to be higher than that in vitro.

Animals↗
PubMed1979

Clinical pharmacology of mephenytoin and ethotoin.

Effective prescribing of anticonvulsants requires foreknowledge of baseline pharmacokinetic data. Little such information is available about the hydantoins other than phenytoin, although one of them, mephenytoin, is widely used. Useful pharmacokinetic data should be derived from patients already exposed to anticonvulsants to reflect the induction of hepatic oxidative enzymes. Single-dose studies of mephenytoin (Mesantoin) and ethotoin (Peganone) were performed in adult inpatients on stable regimens of other anticonvulsants. Five patients received mephenytoin, 7 mg per kilogram of body weight. Serial blood sampling was performed rigorously. The time to peak concentration (Tmax) for mephenytoin was 1 hour, with a half-life (T 1/2) of 7 hours; the T 1/2 of its metabolite, 5-ethyl-5-phenylhydantion, was 96 hours. Ethotoin administration was 25 mg per kilogram in 5 patients. Ethotoin Tmax was 2 hours, with a T 1/2 of 5 hours. Saliva accurately represented the unbound fraction for all three agents. Mean salivary levels (as percentage of total levels) were 61% for mephenytoin, 73% for its metabolite, and 54% for ethotoin. The implications for therapy are that following mephenytoin administration, the metabolite 5-ethyl-5-phenylhydantoin will provide anticonvulsant effectiveness, with its long half-life producing stable blood levels on simple dose schedules. Ethotoin, in contrast, has a short half-life and would require divided daily doses to achieve a steady state. This, rather than pharmacological ineffectiveness, limits its usefulness.

Biotransformation↗
PubMed1979

Evaluation of clorazepate (Tranxene) as an anticonvulsant--a pilot study.

Desmethyldiazepam--providing the long-term anticonvulsant effect when diazepam is given orally--is conveniently administered as clorazepate (Tranxene). In this study, clorazepate was compared to phenobarbital as a secondary anticonvulsant in eight ambulatory, adult outpatients. Stable doses of phenytoin were maintained throughout. Drowsiness was present in all on phenobarbital, but there were no clorazepate-related side effects. Seizure control did not differ for each treatment. Addition of common side effects of phenytoin and phenobarbital limited the attained serum levels of each when used together. Clorazepate doses in the 0.56-mg-per-kilogram range gave desmethyldiazepam levels in the 1.0-microgram-per-milliliter range. Induction of metabolism was suggested by falling desmethyldiazepam levels despite increasing doses. Clorazepate is an effective, nontoxic secondary anticonvulsant.

Adolescent↗
PubMed1978

Pharmacokinetic comparison of tablet and suspension dosage forms of carbamazepine.

The bioavailability of two preparations of carbamazepine--the tablet and a new syrup-was studied in 9 adult male volunteers by measuring saliva and serum levels. Peak time was significantly earlier and peak level significantly higher in serum for syrup as compared to tablet. Levels remained higher for syrup for 12 hr. Saliva was contaminated for up to 2 hr by syrup ingestion, possibly for a half hour by the tablet. Beyond that, saliva/serum ratios remained stable. Saliva level variation was too large for pharmacokinetic studies but acceptable for clinical purposes if sampling was long enough after the last dose.

Adult↗
PubMed1977

Carbamazepine--a double-blind comparison with phenytoin.

In a double-blind crossover study, carbamazepine and phenytoin were compared as single anticonvulsants in 47 patients with focal and major generalized seizures. Each drug provided superior seizure control in about half the patients, but significantly fewer patients had objective side effects while taking carbamazepine. Neuropsychologic testing showed improved performance in cognitive function and emotional status of patients while and carbamazepine. No hematotoxic complications arose, but vigilant follow-up is advised. Mean serum level of carbamazepine was 9.3 microng per milliliter with a suggested therapeutic range of 8 to 12 microng per milliliter reached by eventual doses of 16 to 20 mg per kilogram. Carbamazepine offers an independent choice of improved seizure control with a possibility of fewer side effects.

Adult↗
PubMed1975

Pharmacokinetics of carbamazepine in monkeys following intravenous and oral administration.

The pharmacokinetics of carbamazepine were evaluated in four male rhesus monkeys. A 20-mg/kg dose was administered by intravenous (5-min) infusion and orally (nasal-gastric intubation) in a propylene glycol-ethanol-water solvent. Plasma and urine determinations were performed by GLC. All semilogarithmic intravenous curves exhibited an irregular decay behavior in the first 3-hr period, followed by a linear disappearance phase (T 1/2 equals 1.0-2.4 hr). Urinary excretion measurements confirmed the short elimination half-life and showed that less than 1% of the dose was excreted unchanged. Oral studies also yielded a short elimination half-life (1.0-1.60 hr), which was confirmed by urinary excretion measurements. The oral curves were analyzed pharmacokinetically. The fraction of the dose reaching the systemic circulation ranged between 58 and 87%. Measurable (but insignificant) amounts of drug were found in the feces after intravenous and oral administrations.

Administration, Oral↗
PubMed1975

Anticonvulsant level in saliva, serum, and cerebrospinal fluid.

Levels of four anticonvulsant drugs were measured simultaneously in saliva, spinal fluid, and dialyzed serum, i.e., free drug in serum. The level of diphenylhydantoin and possibly of carbamazepine was the same in the three body fluids. The leves of phenobarbital was the same in spinal fluid and dialyzed serum, but was lower in saliva. The level of primidone was different in each body fluid. The technique is simple (flow of saliva stimulated when the subject chews candle was or Teflon) and will be useful to determine the level of free diphenylhydantoin and carbamazepine, which is more closely related to intoxication or drug failure than is the total level of drug.

Carbamazepine↗
PubMed1975

Flash-heater ethylation of some antiepileptic drugs.

We describe a modification of the MacGee method [Anal. Chem. 42, 421 (1970)] for rapid determination of phenytoin (diphenylhydantoin) in plasma by gas-liquid chromatography, in which an ethylaing reagent is used instead of the more common methylating reagents. With this modification, several N-methylated antiepileptic drugs can be separated from their demethylated metabolites. Our results agree well with those of Butler and Waddell [Neurology 8, 106 (1958)], who showed that in patients receiving the N-methylated compounds mephenytoin and mephobarbital, the N-demethylated products, 5-ethyl-5-phenylhydantoin and phenobarbital are found in higher concentrations in plasma than are their respective parent drugs. The method is also useful for routine determinations of phenobarbital, primidone, and phenytoin in serum, cerebrospinal fluid, or saliva.

Alkylation↗