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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
PubMed1995

Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors.

Drug-drug, drug-food, and drug-disease interactions involving hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are reviewed. The four available HMG-CoA reductase inhibitors-lovastatin, simvastatin, pravastatin, and fluvastatin-have different potentials for drug interactions, probably because of their different pharmacokinetic characteristics. Interactions of some of these cholesterol-lowering agents with cyclosporine, erythromycin, high-dose niacin, or gemfibrozil may produce myopathy with or without rhabdomyolysis. Interactions with other commonly prescribed agents, such as bile acid sequestrants, coumarin anticoagulants, and cardiovascular drugs, may alter the pharmacokinetics of either drug, but the clinical significance is generally minor. Food may affect plasma lovastatin concentrations, systemic pravastatin bioavailability, and the maximum serum concentration (Cmax) and time to achieve Cmax for fluvastatin. Hepatic dysfunction may influence the pharmacokinetics of pravastatin; all HMG-CoA reductase inhibitors are contraindicated in patients with liver disease or unexplained elevations in serum aminotransferases. Severe renal insufficiency may necessitate dosage modification in lovastatin recipients. Renal dysfunction seems to affect the pharmacokinetics of pravastatin, simvastatin, and fluvastatin only minimally, but caution is still warranted. Although the HMG-CoA reductase inhibitors rarely have severe adverse effects, they may interact, in some cases dangerously, with other drugs, with food, and with disease states.

Anticholesteremic Agents↗
PubMed1995

Lack of effect of tacrine administration on the anticoagulant activity of warfarin.

The effect of tacrine administration on prothrombin time was studied in 13 patients receiving prolonged warfarin therapy. After a 3-week baseline period and 5 days of placebo administration, patients received 20 mg tacrine four times daily for 5 days. Prothrombin times were determined during baseline, daily before the morning doses of placebo and tacrine, and 14 days after the last tacrine dose (closeout). Mean (+/- SD) prothrombin times were 16.2 +/- 2.8 seconds at baseline, 15.1 +/- 2.6 seconds during the placebo phase, 15.8 +/- 3.6 seconds during the tacrine phase, and 15.3 +/- 3.6 seconds at closeout, indicating that tacrine has no effect on the anticoagulant activity of warfarin. Alteration of warfarin dosage should not be required in patients receiving concurrent tacrine therapy.

Aged↗
PubMed1995

Practical considerations in anticonvulsant therapy--Part 2.

Epilepsy is, for many patients, a lifelong condition that requires treatment with powerful drugs whose doses must be carefully titrated to avoid both breakthrough seizures and toxicity. The medication regimens used to treat epilepsy are further complicated by the fact that most seizure medications are metabolized in the liver and have the potential for serious pharmacokinetic drug-drug interactions with many other medications. Successful management of epilepsy requires a high degree of cooperation among the patient, the pharmacist, and the treating physician. Such cooperation can ensure that the appropriate treatment and drug preparation are selected, compliance is maintained, and dangerous drug-drug interactions are avoided.

Anticonvulsants↗
PubMed1994

Pharmacokinetic effects of fluvastatin in patients chronically receiving digoxin.

A double-blind, randomized, crossover study assessed the effects of a single 40-mg dose of fluvastatin on the steady-state pharmacokinetics of digoxin in chronically treated patients. After demonstrating consistent digoxin serum concentrations as part of the inclusion criteria, 18 patients received a single dose of either fluvastatin or placebo, with a 1-week washout period between crossover to the other treatment. For each patient, 14 serum samples were drawn and urine collected over 24 hours; all samples were assayed for digoxin using a fluorescence polarization immunoassay. The following pharmacokinetic parameters were determined using noncompartmental techniques: area under the curve for 24 hours (AUC24); time to maximum concentration after digoxin (tmax); maximum concentration after digoxin dosing (Cmax); concentration at 24 hours after fluvastatin or placebo (Cmin); total amount excreted in the urine over 24 hours (U24); and urinary clearance (Clren). The pharmacokinetic data were analyzed for sequence, patient nested with sequence, and period and treatment differences using ANOVA, Schuirmann's two one-sided testing approach, confidence intervals, and power analysis. The AUC24, Cmax, and tmax for digoxin were considered bioequivalent with the two treatments. The differences in Cmax, U24, and Clren were statistically significant but were not considered to be clinically relevant due to the low magnitude of the difference (< 20%). There were no clinically significant adverse reactions attributable to either digoxin or fluvastatin.

Aged↗
PubMed1993

Efficacy, safety, and cost issues in managing patients with gastroesophageal reflux disease.

The phases of therapy for gastroesophageal reflux disease (GERD) and the efficacy, safety, and cost of the various drugs used are discussed. The therapeutic goals for patients with GERD are to relieve pain, promote healing, avoid complications, and prevent recurrence. Sustained inhibition of gastric acid secretion is necessary to facilitate healing of eroded esophageal mucosa. Phase 1 treatment involves lifestyle changes to remove factors that may help to precipitate reflux, such as overeating, alcohol, and tobacco. Phase 2 involves pharmacologic manipulation of the secretion, concentration, and transport of gastric acid. The drugs used are antacids, alginic acid, the histamine H2-receptor antagonists, the prokinetic agents, sucralfate, and omeprazole. While all of these agents may provide symptomatic relief, only the H2 antagonists and omeprazole have been convincingly shown to relieve symptoms and promote healing. The H2 antagonists differ in potency, pharmacodynamic effect, pharmacokinetics in certain patient groups, drug interactions, and adverse effects. The H2 antagonists may not be effective at standard dosages in patients who secrete especially large quantities of gastric acid. Because of its mechanism of action, omeprazole provides greater inhibition of gastric acid than any other antisecretory drug. Omeprazole may also be the most cost-effective treatment. The availability of omeprazole may reduce the number of patients for whom clinicians must resort to phase 3 treatment, surgery. Although many drugs provide symptomatic relief in patients with GERD, the healing that is necessary to break the cycle of damage and symptoms is promoted only by the H2 antagonists and omeprazole.

Alginates↗
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↗