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Biomedical subjects

W R Garnett

Publications and source records attributed to W R Garnett.

At least 19 recordsLinked to original sources
PubMed1992

Comparative bioavailability and steady state fluctuations of Tegretol commercial and carbamazepine OROS tablets in adult and pediatric epileptic patients.

The comparative bioavailability and steady state fluctuations resulting from the administration of Tegretol 200 mg commercial tablets and carbamazepine OROS controlled delivery tablets were investigated in 22 adult and 12 pediatric epileptic patients. Tegretol commercial tablets were dosed according to previously established clinical regimens of 400 to 2000 mg daily doses divided into four equal or unequal intervals. Carbamazepine OROS was dosed every 12 h at the same corresponding daily dose. Comparisons of the pharmacokinetic parameters AUC, Cmax, Cmin, and tmax at steady state for the two dosage forms demonstrated definitively the bioequivalence of carbamazepine OROS with Tegretol commercial tablet over a 24-h treatment interval.

Adolescent↗
PubMed1991

Current issues in the treatment of epilepsy.

General principles of antiepileptic drug (AED) therapy are reviewed, current issues involving the use and monitoring of AEDs are examined, promising investigational agents are briefly reviewed, and situations that require potentially difficult decisions about long-term care are discussed. The initial treatment should be monotherapy with a first-line AED for the particular seizure disorder. The usual approach is to maximize seizure control and minimize the adverse effects of AED therapy. Current issues involving the pharmacokinetics, use, and monitoring of the conventional AEDs phenytoin, phenobarbital, primidone, carbamazepine, valproic acid, ethosuximide, benzodiazepines, and acetazolamide are discussed. AED therapy may have adverse effects on behavior and cognition. The risk of teratogenicity with well-monitored AED therapy is probably low, and severe hepatotoxicity is uncommon. Because carbamazepine, phenobarbital, phenytoin, and primidone all have enzyme induction properties, a number of clinically important interactions are possible. Issues related to discontinuing AED therapy, serum concentration monitoring, and generic interchange of AED products are addressed. Whether AEDs should be used to prevent recurrent febrile seizures, alcohol withdrawal seizures, or seizures in patients with head trauma or stroke must be considered. The treatment of seizure disorders is a complex process involving identification of the seizure disorder, selection and monitoring of an appropriate AED(s), and consideration of adverse effects and drug interactions. Whether therapy should be discontinued after a prolonged seizure-free period, compliance issues, and whether to treat certain conditions prophylactically also must be considered.

Anticonvulsants↗
PubMed1990

Loss of carbamazepine suspension through nasogastric feeding tubes.

The apparent loss of carbamazepine suspension during administration through polyvinyl chloride nasogastric feeding tubes in vitro was studied. Twelve methods of administering carbamazepine suspension (100 mg/5 mL) were tested; the methods differed with respect to nasogastric tube size, presence and type of diluent, and type of flush solution. Undiluted or 50% diluted carbamazepine suspension 200 mg was drawn up in a syringe and forced through adult or pediatric nasogastric feeding tubes. The tubes were immediately flushed twice with 50 mL of sterile water, 0.9% sodium chloride solution, or 5% dextrose solution, by using the same syringe used to administer the suspension. Samples were collected and analyzed for carbamazepine concentration by high-performance liquid chromatography. Each administration method was tested six times, and the results were subjected to analysis of variance. Significant loss of carbamazepine was noted for four of the six methods in which undiluted suspension was administered. In these methods, adult and pediatric tubes were flushed with sterile water or 0.9% sodium chloride. No significant loss of drug occurred for any of the methods involving the use of diluent. Significant losses were associated with diluent and flush solution but not nasogastric tube size. Carbamazepine suspension should be mixed with an equal volume of diluent before being administered through nasogastric feeding tubes.

Carbamazepine↗
PubMed1989

The effect of everyday exercise on steady state digoxin concentrations.

The purpose of this study was to evaluate the effect of 1 hour of everyday exercise (walking at patient's own pace) on serum digoxin concentrations. Nine white male subjects (ages 58-74) who had been taking the same digoxin dose for greater than 1 month participated. There were three continuous phases: 1 hour of rest, 1 hour of exercise, and a final hour of rest. Serum digoxin concentrations were drawn every 20 minutes. During the first rest period, serum digoxin concentrations rose 30% from the first concentration drawn in the study. After 1 hour of exercise, serum digoxin concentrations fell 26.8% from the last concentration of the first rest period. At the end of the second hour of rest, serum digoxin concentrations increased by 36.6% from the last concentration. Repeated measures analysis of variance demonstrated a significant (P less than .01) change in serum digoxin concentrations. Significant (P less than .01) differences were found between sampling times 0 and 60, 60 and 80, 60 and 100, 60 and 120 and 180 minutes using a paired t-test with Bonferroni correction. A weak correlation (r = 0.74, r2 = 0.55) between percent change in concentrations and age during the exercise phase was found, but there was no correlation between the percent change in concentrations and age during the two immobilization phases. Because significant changes in concentrations occurred during each phase of the study, we conclude that the influence of everyday exercise should be taken into account when interpreting serum digoxin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1989

Cardiovascular effects of H2-receptor antagonists.

The type II histamine receptor antagonists, cimetidine and ranitidine, widely used in treatment of peptic ulcer disease have been reported to cause bradycardia. To evaluate the cardiovascular effects of H2 antagonists nineteen healthy volunteers were entered into a double-blind crossover comparison of cimetidine 300 mg qid, ranitidine 150 mg bid, and placebo. Subjects ingested study medicine for 7 days prior to being tested by the Bruce Exercise Test. Heart rate, blood pressure, oxygen consumption, expiratory volume, and fractional expiration of CO2 and O2 were measured at rest, exercise and recovery. A plasma sample for determination of cimetidine and ranitidine levels were obtained prior to the exercise period. Multivariate analysis and paired t test revealed no significant differences for the cardiovascular or pulmonary variables. However, in 5 subjects, the heart rate at 25% maximum VO2 was depressed 8% (P less than or equal to 0.03). This effect in a small percentage of the population suggests that further studies are needed to determine if subpopulations are affected.

Adult↗
PubMed1989

Usefulness of a single-dose prediction model for the determination of long-term maintenance therapy of valproic acid.

The single-dose prediction model (SDPM) of Slattery et al. has been shown accurately to predict short-term (3 to 7 days) steady-state valproic acid (VPA) concentrations in normal volunteers and in hospitalized patients receiving monotherapy. To assess the long-term usefulness of the SDPM in a real-life clinic setting, six ambulatory patients ranging in age from 2 to 8 years were studied. Blood samples were drawn at least 6 h after the initial dose but before the second dose of VPA, A steady-state trough concentration (Cminss) was measured 3 to 7 days after the initiation of therapy. Dosage adjustments and alterations in therapeutic regimen were allowed and another Cminss was measured after 1 to 12 months. Predicted Cminss values were calculated for both the short-term and long-term VPA regimens. Predictive performance analysis demonstrated that the SDPM was unbiased in predicting both short-term and long-term VPA Cminss values and precise in predicting only short-term VPA Cminss values. The SDPM is not a reliable predictor of long-term total VPA concentrations in seizure patients in an outpatient clinic setting.

Child↗
PubMed1989

The effects of storage and shaking on the settling properties of phenytoin suspension.

Phenytoin suspension (PHY-S) is reported to settle, resulting in uneven drug distribution and variable patient dosing. We designed this study to determine the rate of settling and the amount of agitation needed to resuspend the preparation. To determine the rate of settling, we thoroughly shook three bottles of PHY-S and then left them undisturbed. We took samples from the top and bottom of each bottle with a microsyringe at 15 minutes, 1, 6, 12, 24, 48, and 72 hours, and 1, 2, 3, 4, and 5 weeks. We simulated patient administration with daily doses that were measured under good, fair, and poor shaking techniques. We analyzed samples after every tenth dose. After complete resuspension the active ingredient in PHY-S settles at a very slow rate. We found no differences in concentration between the top and bottom until the fifth week in the bottles thoroughly shaken and left undisturbed. Minimal agitation is required to resuspend PHY-S. The well-shaken and poorly shaken bottles in the patient simulation phase exhibited no differences in concentrations whereas the unshaken bottle had differences throughout the study period. Problems thought to be associated with PHY-S may be related to compliance and inaccurate measuring devices.

Drug Storage↗
PubMed1989

Recovery of warfarin from an enteral nutrient formula.

The in vitro recovery of warfarin from an enteral nutrient formula after filtration to remove the protein-bound fractions was determined. This study was conducted in two parts. In part 1, 0.25-, 0.50-, and 1-mL aliquots of warfarin sodium stock solution were added to 150 mL of the enteral nutrient formula Osmolite under physiologic conditions to produce warfarin concentrations of 16.7, 33.3, and 66.7 micrograms/mL. In part 2, a 0.5-mL aliquot of the warfarin sodium stock solution was added to Osmolite 100 mL-distilled water 50 mL, Osmolite 75 mL-distilled water 75 mL, and Osmolite 150 mL. The samples were filtered through a membrane that retained macromolecules while allowing warfarin to pass through, and the warfarin concentration was measured by high-performance liquid chromatography. Assays of protein-free buffered control solutions of warfarin before and after filtration indicated that no significant amount of warfarin was retained in the filtration membrane. Significantly less warfarin was recovered from full-strength Osmolite after filtering than before filtering at all warfarin concentrations tested. Significantly more warfarin was recovered from the Osmolite-distilled water solutions than from the undiluted Osmolite. These results suggest that there is some sequestering of warfarin in the macromolecular fraction of the enteral nutrient formula. The decreased recovery of warfarin from the enteral nutrient formula used in this study has potential clinical importance, but further research in humans is needed to substantiate these in vitro observations.

Chromatography, High Pressure Liquid↗
PubMed1989

Concentration uniformity of extemporaneously prepared ranitidine suspension.

The concentration uniformity of an extemporaneously prepared ranitidine suspension was studied. To prepare the ranitidine suspension, 36 150-mg tablets were pulverized and suspended in 180 mL of distilled water. This mixture was diluted with simple syrup to a total volume of 360 mL, resulting in a final ranitidine concentration of 150 mg/10 mL. Samples from each of three bottles that had been filled with 60 mL of the suspension were assayed for ranitidine content by high-performance liquid chromatography. The sedimentation of suspended ranitidine tablet particles was studied by visual observation of the setting process in 10-mL samples from the same batch. The overall mean concentrations (in milligrams per milliliter) of ranitidine were 14.53, 15.25, 13.92, 12.67, and 12.72 at 0, 3, 7, 14, and 21 days, respectively. Compared with baseline, the difference in the ranitidine concentration was not significant over days 0-7. The ranitidine concentration was significantly reduced during the following time intervals: days 0-14, days 0-21, and days 7-21. In the settling experiments, the mean time (+/- S.D.) for sediment to first appear on the test tube bottom was 14.67 +/- 5.35 seconds. Approximately 40-50% (mean level = 3.2 mm) of the total sedimentation level (mean level = 7.3 mm) was observed one minute after shaking. The uniformity of ranitidine suspensions compounded according to procedures described in this report possibly could be improved with sonication. The ranitidine suspension should be well shaken, the dosage should be measured immediately after shaking, and the suspension should be used within seven days of compounding.

Chemistry, Pharmaceutical↗
PubMed1989

Stability of carbamazepine suspension after repackaging into four types of single-dose containers.

The stability of carbamazepine in commercially available suspension that had been repackaged in various single-dose containers was studied. Carbamazepine suspension was repackaged in 2-mL and 8-mL aliquots in amber glass vials, polypropylene vials, and amber polypropylene syringes and in 2-mL aliquots in amber glass oral syringes. Containers were stored at room temperature and continuously exposed to fluorescent light for up to 12 weeks. Samples from each container type and volume were assayed for carbamazepine content by high-performance liquid chromatography at various intervals during storage. Carbamazepine concentrations in the samples were compared with the carbamazepine concentration in the original manufacturer's container. The pH of the samples was also determined, and the suspensions were inspected for color, odor, and large particles. There was no significant decrease in carbamazepine concentration of more than 10% in samples stored for up to eight weeks. After 12 weeks, significant decreases in concentration were observed in all but one container type. No changes in color, odor, or consistency were observed during the 12 weeks, and there were no significant changes in pH. In commercially available suspension repackaged in volumes corresponding to common pediatric doses, carbamazepine (20 mg/mL) is stable for at least eight weeks when stored at room temperature in the containers tested.

Carbamazepine↗
PubMed1988

Ranitidine accumulation in patients undergoing chronic hemodialysis.

Ranitidine accumulation was assessed in 20 patients undergoing chronic hemodialysis following oral daily doses of 150 mg ranitidine for 10 days. Serum ranitidine concentrations prior to dialysis were 191 +/- 115 mcg/l and 207 +/- 172 mcg/l for patients dialyzed three and two times per week, respectively. The amount of ranitidine recovered in the dialysate during the final dialysis session of the study was negligible and ranged from 308-3036 mcg, representing less than 3% of the administered dose. Clearance by hemodialysis was 3.0 +/- 1.1 l/hr. Once daily dosing of 150 mg ranitidine does not result in excessive accumulation, and drug loss during hemodialysis is small. These data suggest that supplemental dosing after hemodialysis is not indicated.

Adult↗
PubMed1988

Sulindac-induced toxic epidermal necrolysis.

A case of sulindac-induced toxic epidermal necrolysis (TEN) is described; the etiology, symptoms, and treatment of TEN are reviewed; and sulindac's pharmacokinetic characteristics and other adverse effects are discussed. A 62-year-old black woman was given a prescription for sulindac 150 mg twice daily to relieve pain associated with degenerative joint disease. She also had a nine-year history of type II diabetes mellitus that was being managed with tolbutamide 500 mg once daily. After two weeks of sulindac therapy she developed a rash that spread over her entire body. Sulindac therapy was discontinued, and one day later the patient was admitted to the hospital with a temperature of 104.6 degrees F, conjunctivitis, and an erythematous macular rash over 60% of her body. Initially, therapy included prednisone 160 mg orally every day, applications of silver sulfadiazine cream four times daily for two days, and methylcellulose 0.5% ophthalmic solution (two drops four times daily) for the conjunctivitis. She also received intravenous hydration. By the fifth hospital day the patient's skin lesions and conjunctivitis had improved to the point that the prednisone dosage was tapered to 120 mg, then to 80 mg, and then to nothing over the following three days. Her diabetes was managed by short-term treatment with NPH insulin; however, before discharge, tolbutamide therapy was reinstituted, and insulin was discontinued. At follow-up four weeks after discharge, the patient's skin was largely clear. TEN has multiple etiologies, but the basic mechanism of injury is believed to be an immunological reaction directed at the basal cell layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1987

Phenytoin removal during plasma exchange.

Plasma exchange is currently being used to treat a variety of disorders including immune complex and hematologic disorders. It has been shown that the removal of plasma removes drugs bound to plasma proteins. This case documents the removal of phenytoin during plasma exchange therapy. Total and free phenytoin serum concentrations were obtained before and after each exchange. Aliquots were obtained from each pass, and total phenytoin concentrations were determined. The total phenytoin serum concentration increased during the first exchange, while the total concentration decreased as a result of the second exchange. It was determined that approximately 27.7 mg and 30.4 mg of phenytoin were removed by the first and second plasma exchanges, respectively.

Adolescent↗
PubMed1987

A comparative bioavailability study of carbamazepine tablets and a chewable tablet formulation.

Differences in product formulations have been shown to affect the therapeutic response by altering the relative bioavailability and pharmacokinetics of a drug. The relative bioavailability and pharmacokinetics of carbamazepine tablets (CBZ) and a chewable tablet formulation were evaluated in 10 normal healthy subjects (five men and five women). The study utilized a randomized, crossover design with a 4-week washout period between doses. Blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 10, 14, 24, 30, 36, and 48 h following a 200-mg dose. Plasma samples were assayed by fluorescence polarization immunoassay. Ke, Cmax, Tmax, area under the curve (AUC), and relative bioavailability were estimated using traditional pharmacokinetic methods and compared by paired t test. A statistically significant higher Cmax (3.81 +/- 81 vs. 4.64 +/- .80 mg/L) was observed with the chewable tablet formulation but was not thought to be clinically relevant. No significant differences between formulations for Ke (0.022 +/- 0.007 vs. 0.025 +/- 0.008 h-1 h), Tmax (7.49 +/- 2.69 vs. 6.04 +/- 2.7 h), AUC 48 h (119 +/- 22 vs. 133 +/- 13 mg/h/L), or AUCO--infinity ( 221 +/- 40 vs. 203 +/- 41 mg/h/L) were noted. Absorption was variable for both preparations. The relative bioavailability using the tablet as the standard formulation was (0.92 +/- 0.22). Transient, mild side effects were noted in three subjects with the chewable tablet alone, and one subject experienced side effects with both formulations. It was concluded that CBZ tablets and chewable tablets may be used interchangeably; however, considerable intra- and intersubject variability exists, and the need for patient monitoring is emphasized.

Adult↗
PubMed1987

The clinical pharmacist in drug research and development: the publication record.

A viable discipline requires the generation of new information. Clinical pharmacists have recognized that their success depends on their ability to contribute to (Table: see text) the expansion of the body of knowledge of their discipline. They have developed practice and research programs in a variety of areas. One of the results of these programs is the publication of articles in a variety of pharmacy and medical journals. Clinical pharmacists with specialty interests publish in journals that represent those interests. In comparing the type of clinical pharmacists' publications in the area of drug development, it is also clear that they are most suited for research in the clinical phase; that is, clinical pharmacists conduct research on the pharmacokinetics, pharmacodynamics, and safety and efficacy of new and old drugs. Clinical pharmacists tend to be members of research teams but bring a unique perspective to the team. In their collaboration with physicians, basic scientists, and other health-care personnel, clinical pharmacists are often cited as first author. Their research is important to researchers with similar specialty interests, regardless of whether they are pharmacists. Data retrieval has developed so that researchers with similar interests can identify key publications wherever they are published. Articles published by clinical pharmacists in pharmacy journals are quoted by other researchers. Therefore, I conclude that a number of clinical pharmacists are active in drug research and development. Many of these pharmacists were trained as practitioners, but have developed into researchers through trial and error and hard work.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacists↗
PubMed1986

Diphenhydramine.

Explore the source record for details and available documents.

Adult↗
PubMed1986

Influence of tube type, storage time, and temperature on the total and free concentration of valproic acid.

The influence of storage conditions on the total and free concentration of valproic acid (VPA) was studied in six normal male subjects who ingested 750 mg of VPA (3 X 250 mg Depakene capsules; Abbott Laboratories). Blood samples were collected in various types of Vacutainer tubes (red top, no additives; green top, sodium heparin; blue top, sodium citrate; and purple top, EDTA) 2 h post administration of VPA. Either these samples were centrifuged immediately or stored for various periods of time at room temperature or refrigerated, or the supernate was frozen prior to analysis. Free VPA samples were obtained utilizing the Amicon ultrafiltration system. All VPA samples were analyzed by gas-liquid chromatography. Total VPA concentrations obtained from plasma collected with sodium citrate were lower (p less than 0.05) than either serum or plasma collected with other anticoagulants. There were no differences (p greater than 0.05) in total or free VPA concentrations between samples collected in serum or in plasma collected with heparin or EDTA. Storing samples for 96 h at room temperature did not alter the total VPA concentrations but was found to increase the free fraction of VPA (p less than 0.05). The refrigeration or freezing of the supernate from the blood samples for 7 days did not alter (p greater than 0.05) the total or the free fraction of VPA. The results of this study demonstrate that total and/or free VPA may be collected from either serum or plasma, provided sodium citrate is not used to collect plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Specimen Collection↗