W R Garnett

Virginia Commonwealth University, Richmond, VA, United States

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Publications (73)168.82 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The nicotine bolus theory states that the dependence-producing potential of cigarettes relates to a rapid increase in nicotine at brain receptor sites. It has been suggested that ammonia, a compound typically found in tobacco products, further increases the amount of nicotine absorbed and its absorption rate. The aim of this study was to determine whether different ammonia yields in cigarettes affected the rate or amount of nicotine absorption from the lungs to arterial circulation. 34 adult smokers received 3 separate puffs from each of 2 test cigarettes with different ammonia yields (ammonia in smoke: 10.1 μg per cigarette vs. 18.9 μg per cigarette), followed by rapid radial arterial blood sampling (maximum one sample per second) with 30 min between puffs. Arterial blood samples were assayed for nicotine by liquid chromatography tandem mass spectrometry. Pharmacokinetic modeling was performed and the two test cigarettes were assessed for bioequivalence. No significant differences were found in area under the curve, C(max), or T((max)) and the 2 test cigarettes were found to be bioequivalent based on 2 one-sided tests at a significance level of 5%. In addition, the zero-order rate constant (k(0)) obtained from the initial slope of the curves and the model-dependent first-order rate constant (k(a)) were not significantly different. This study provides strong evidence that the different ammonia yields of the test cigarettes had no impact on nicotine pharmacokinetics; thus, the ammonia did not increase the rate or amount of nicotine absorption from a puff of cigarette smoke.
    Nicotine & Tobacco Research 12/2011; 14(5):586-95. · 2.48 Impact Factor
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    ABSTRACT: Rectal administration of diazepam (DZ) has been used effectively in patients with epilepsy who experience acute repetitive seizures, but rectal gel may be difficult to administer during a seizure and is subject to variable drug absorption. An intramuscular (IM) autoinjector DZ formulation may offer a practical alternative to rectal DZ. This single-center, open-label, 3-treatment, 3-period crossover study compared the pharmacokinetic and safety profiles of 10mg DZ administered rectally in 24 healthy, fasted and fed subjects versus IM autoinjector delivery in fasted subjects. Blood samples were collected at baseline and for up to 24h postdose and plasma DZ concentrations were determined by liquid chromatography and tandem mass spectrometry. There were no significant differences between plasma concentrations for rectal administration of DZ in fasted and fed subjects at any time point. Intramuscular DZ administration resulted in more rapid and less variable drug absorption than rectal delivery. At 30min postdose and at all subsequent evaluations, IM administration resulted in significantly higher areas under the curve versus rectal administration in fasted subjects (p<0.05). This significant difference was sustained throughout the remainder of the 24-h study period (p<0.05). All reported adverse events were considered mild, and none required treatment.
    Epilepsy research 01/2011; 93(1):11-6. · 2.48 Impact Factor
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    ABSTRACT: We developed an automated sampling system to allow multiple, discrete blood samples from a human participant to be collected rapidly and immediately following cigarette smoke exposure. We reported the details of the sampling system along with the results of a pilot study for evaluation of the system. Components of the system include silastic tubing, solenoid pinch valves, a peristaltic pump, and a fraction collector. This system incorporates a smoking machine that allows precise delivery of cigarette smoke through a mouthpiece and intricate timing to correlate blood samples with smoke inhalation. All components are controlled via integration from a user interface and are fully customizable. We performed several tests to evaluate the equipment, including tubing dead volume, leakage tests, and sample reproducibility. We also performed a pilot study with 6 adult smokers, who received 6 controlled puffs of a research test cigarette. Each inhalation was followed by radial arterial blood collection (1 sample per second tapered to 1 sample every 4 s) for 1 min. Samples were evaluated for nicotine via liquid chromatography-tandem mass spectrometric methods. Sampling times and volumes were sufficient for nicotine analysis. No adverse effects were seen in the pilot study, and a 30-min washout period was deemed appropriate between puffs. A significant rise in plasma nicotine levels above baseline after inhalation of smoke was consistently detected in all participants. The unique advantage of this system is to allow rapid blood sampling after a puff of cigarette smoke, with the benefits of reproducibility, reduction in labor intensity, and high temporal resolution.
    Nicotine & Tobacco Research 02/2010; 12(4):319-25. · 2.48 Impact Factor
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    ABSTRACT: The goal of epilepsy therapy is to help patients achieve seizure freedom without adverse effects. While monotherapy is preferable in epilepsy treatment, many patients fail a first drug due to lack of efficacy or failure to tolerate an initial medication, necessitating an alteration in therapy. Sudden changes between monotherapies are rarely feasible and sometimes deleterious given potential hazards of acute seizure exacerbation or intolerable adverse effects. The preferred method for converting between monotherapies is transitional polytherapy, a process involving initiation of a new antiepileptic drug (AED) and adjusting it toward a target dose while maintaining or reducing the dose of the baseline medication. A fixed-dose titration strategy of maintaining the baseline drug dose while titrating the new medication is preferable when breakthrough seizures are occurring and no adverse effects are present. However, a flexible titration strategy involving reduction of the baseline drug dose to ensure adequate tolerability of the new adjunctive medication is preferred when patients are already experiencing adverse effects. This article reviews pharmacokinetic considerations pertinent for ensuring successful transitional polytherapy with the standard and newer antiepileptic drugs. Practical consensus recommendations "from an expect panel (SPECTRA, Study by a Panel of Experts Considerations for Therapy Replacement and Antiepileptics) for a successful monotherapy" AED conversions are then summarized. Transitional polytherapy is most successful when clinicians appropriately manage the titration strategy and consider pharmacokinetic factors germane to the baseline and new adjunctive medication.
    DNA research: an international journal for rapid publication of reports on genes and genomes 06/2009; 7(2):83-95. · 1.73 Impact Factor
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    ABSTRACT: To develop expert consensus for conversion between antiepileptic drug (AED) monotherapies, an 11-member panel used the Delphi Technique over three rounds to: (1) identify relevant issues, (2) vote on the issues, and (3) develop consensus. The panel agreed on the basic principle to taper the existing AED only after a presumably efficacious dose of the planned AED was reached. Application is modified by adverse effects possibly attributable to the existing drug, in which case earlier or more rapid tapering of the existing drug should be considered. Patients with uncontrolled seizures, as well as seizure-free patients for whom driving privileges are a consideration, may benefit from slower tapering by smaller dosage decrements of the existing AED. For 10 of the 12 AEDs considered, the panel made titration recommendations concerning initial and target doses for the planned AED, supplementing limited data in the prescribing information. This expert guidance will aid in the period of transitional polytherapy with AEDs from monotherapy to monotherapy.
    Epilepsy & Behavior 10/2007; 11(2):222-34. · 1.84 Impact Factor
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    ABSTRACT: Divalproex sodium extended-release (Depakote ER) is a once daily (QD) formulation for valproic acid that was developed to improve patient compliance and to reduce side effects compared with the standard twice-daily (BID) delayed release (DR) formulation (Depakote tablets). However, there are concerns of potential sub-therapeutic concentrations following delayed or missed doses or toxic concentrations with replacement doses for the ER and DR formulations. Simulations can be used to investigate the effect of poor compliance on drug concentrations, which may not be possible to do in a study population for ethical or practical reasons. Using Monte Carlo simulations, the effect of different patterns of poor compliance on ER QD and DR BID were systematically characterized. Non-linear binding of valproic acid to albumin was incorporated into the model, and the results were based on total and unbound VPA for comparison. The effect of poor compliance is less significant on DR BID compared with ER QD. Dosing recommendations in the case of a missed or delayed dose are both formulation and dose dependent. Since total VPA concentrations show higher inter-individual variability and tend to under-estimate the effect of poor compliance; the use of unbound VPA concentrations may offer an advantage in therapeutic monitoring.
    Biopharmaceutics & Drug Disposition 01/2006; 26(9):417-25. · 2.09 Impact Factor
  • William R Garnett
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    ABSTRACT: To review and evaluate the medical literature concerning antiepileptic drug (AED) therapy in elderly patients. A MEDLINE search (1982-December 2004) was conducted. Bibliographies of the articles identified were also reviewed, and an Internet search engine was used to identify additional pertinent references. Clinical studies and reviews were evaluated, and relevant information was included. The elderly have the highest incidence of seizures among all age groups. Complex partial seizures are the most common, followed by primary generalized tonic-clonic seizures. An accurate diagnosis may prove difficult because of a low suspicion of epilepsy in the elderly and other diseases that may mimic seizures. Most AEDs are approved for treatment of elderly patients who have partial and tonic-clonic seizures. However, a number of age-related variables should be addressed when selecting an appropriate AED. Age-dependent differences in pharmacokinetics and pharmacodynamics of AEDs must be taken into account. Drug-drug interactions must be considered since elderly people often take multiple medications. The ultimate factor that often determines AED selection is tolerability. Numerous factors must be considered in treating elderly patients for seizures, but maximizing the ability of patients to tolerate drug therapy is often the basis for AED selection. Special consideration should be made along several lines, including elderly patients' cognitive functioning and their tendency to respond to lower AED concentrations.
    Annals of Pharmacotherapy 12/2005; 39(11):1852-60. · 2.57 Impact Factor
  • Alaa Ahmad, William R Garnett
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    ABSTRACT: Plasma concentrations of antiepileptic drugs (AEDs) can vary and are not always an indication of clinical utility. However, adverse event occurrence can be correlated to fluctuations in plasma drug levels that occur with varying dosing regimens of the many AEDs. In this study, we present the results of computer simulations of plasma concentrations of the AEDs carbamazepine (CBZ) extended-release capsules (CBZ-ERC) (Carbatrol) and oxcarbazepine (OXC). A one-compartment open model with first-order absorption and elimination was generated from the results of a previous study measuring plasma concentrations following one 400 mg fasting dose of CBZ-ERC. This model was used to simulate plasma concentrations of CBZ following multiple 400 mg doses of CBZ-ERC at 12-hour intervals, and then when a missed dose is taken 3, 6, or 9 hours late; when two doses are taken at one time; and when a single dose is taken at the time of the next dosing. In comparison, similar modeling was done for monohydroxy derivative (MHD) of OXC at doses of 600 or 1200 mg. Plasma drug concentrations after 24 hours without medication were 4.1 mg/L for CBZ-ERC, 8 mg/L for 600 mg OXC, and 16 mg/L for 1200 mg OXC. If a patient was to take only a single dose 24 hours late, it would take 24 hours to reach steady-state trough values for CBZ-ERC, 36 hours for 600 mg OXC, and 2 days for 1200 mg OXC. The trough plasma concentration following a missed dose and the peak plasma concentration following a double dose (administered 12 hours after the missing of a dose) differed by a factor of two in the CBZ-ERC simulation, compared with a factor of three in both OXC simulations. The ultimate goal of antiepileptic therapy is a seizure-free state without side effects. The current computer simulation study indicates that AEDs such as CBZ-ERC and OXC, which produce relatively stable plasma concentrations, should be useful in attaining this goal. Nonetheless, simulated plasma concentrations resulting from CBZ-ERC treatment tended to oscillate less dramatically compared with simulated plasma concentrations resulting from treatment with 600 or 1200 mg OXC.
    Current Medical Research and Opinion 10/2005; 21(9):1363-8. · 2.37 Impact Factor
  • William R Garnett, Thomas D Gilbert, Paul O'Connor
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    ABSTRACT: Although generic formulations of immediate-release carbamazepine (IR-CBZ) are available, extended-release delivery systems may offer important advantages, including the convenience of less-frequent administration and smaller peak-to-trough serum carbamazepine (CBZ) fluctuations. The aim of this study was to compare the patterns of pharmacotherapy, rates of adverse events, and the utilization costs among patients treated with the available CBZ formulations (ie, generic and branded IR-CBZ, and extended-release CBZ (ER-CBZ) capsules [Carbatrol, Shire US Inc., Wayne, Pennsylvania] and tablets [Tegretol-XR, Novartis Pharmaccuticals Corporation, East Hanover, New Jersey]). Data were retrieved from the PharMetrics patient-centric database (which contains integrated claims data for almost 36 million unique patients from 61 US health plans) for patients who were diagnosed with epilepsy and initiated CBZ between July 1999 and June 2001. Patient demographic and clinical characteristics, adverse events, discontinuations, CBZ therapy switches, and utilization and costs for related care subsequent to treatment initiation were recorded. Annual rates of adverse events and discontinuations were calculated, and the risks of these events were compared across treatment groups. Data were gathered for 1737 patients. The branded CBZ group was demographically and clinically different than the other groups (ie, migraine and cerebral palsy prevalence) and therefore was excluded from event-risk analyses. Results of the proportional hazards regression analysis indicated that Tegretol-XR patients were more likely to experience common central nervous system (CNS)-related adverse events relative to Carbatrol (hazard ratio, 1.67; P = 0.043). A lower percentage of subjects switched off ER-CBZ relative to IR-CBZ (Carbatrol, 5.2%; Tegretol-XR, 5.7%; generic IR-CBZ, 13.0%; branded IR-CBZ, 16.7%). Differences in mean payments for epilepsy-related health care services at 1 year among Carbatrol, Tegretol-XR, and branded or generic CBZ did not reach statistical significance. Among the available CBZ formulations, Carbatrol was associated with a lower incidence of common CNS adverse events. ER-CBZ formulations were also associated with reduced likelihood of therapy discontinuation or switching CBZ medications, relative to patients taking generic IR-CBZ, in this retrospective data analysis.
    Clinical Therapeutics 08/2005; 27(7):1092-103. · 2.23 Impact Factor
  • Alaa Ahmad, William R Garnett
    Clinical Drug Investigation 02/2005; 25(10):669-73. · 1.70 Impact Factor
  • William R Garnett
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    ABSTRACT: In the hospital setting, prophylactic acid suppression is an important part of care for many critically ill patients. It may also prevent rebleeding in patients admitted with acute upper gastrointestinal tract bleeding. Effective treatments for these conditions stemmed from our increased understanding of the gastric acid secretory pathway and target pH values. The late 1970s saw the introduction of histamine2-receptor antagonists (H2RAs), which partially suppress basal and meal-stimulated acid secretion. Some of these agents can induce an intragastric pH greater than 3, lasting for approximately 10 hours/day when given twice/day at recommended doses. This level of acid suppression can facilitate healing of duodenal ulcers but has limited efficacy for other indications (e.g., gastrointestinal bleed). In the late 1980s a more potent class of acid-suppressing agents was developed, proton pump inhibitors (PPIs). The PPIs can induce an intragastric pH above 3 lasting for approximately 17 hours/day, and an intragastric pH above 5 for approximately 9 hours/day after once-daily oral administration of recommended doses. It is possible to attain even higher target pH values with large doses and with continuous intravenous infusion. Thus, PPIs are agents of choice for treatment of many acid-related disorders including peptic ulcer disease and moderate-to-severe gastroesophageal reflux disease, and for prevention of rebleeding in patients with upper gastrointestinal bleeding. Availability of an intravenous formulation, pantoprazole, enables hospitalized patients for whom oral administration is not feasible to benefit from the superior potency of PPIs. Preliminary data suggest that intravenous PPIs may be more effective than H2RA prophylaxis against stress-related ulcer bleeding for intensive care patients and should facilitate healing in those with bleeding ulcers of the upper gastrointestinal tract.
    Pharmacotherapy 11/2003; 23(10 Pt 2):56S-60S. · 2.31 Impact Factor
  • R Edward Hogan, William R Garnett, Vijay M Thadani
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    ABSTRACT: An earlier 6-month, multicenter, open-label study in patients with complex partial seizures found that a switch from multiple daily doses of conventional carbamazepine (CBZ) to twice-daily CBZ extended-release capsules(CBZ-ERC) was well tolerated, with maintenance of seizure control over the study period and significant improvements in quality of life (P < 0.001). The goal of the present study was to assess the tolerability and effects on quality of life of twice-daily CBZ-ERC over the longer term in patients with seizure disorders. This was a multicenter, open-label assessment of the long-term(12-36 months) tolerability and quality-of-life effects of twice-daily CBZ-ERC given at a daily dose equivalent to the daily dose of CBZ taken before study en-try. The regimen could be adjusted as clinically indicated up to a daily dose of 1600 mg. Patients could receive up to 2 other antiepileptic drugs during the study. One hundred eighteen patients were enrolled. In patients completing>12 months of study therapy, a significant decrease in the highest mean 2-day frequency of generalized tonic-clonic seizures was observed over the first 12 months (P = 0.005). The significant improvements in quality of life achieved in the earlier study were maintained during the present study. Of 37 patients who were discontinued from the study, 9 met criteria mandating withdrawal from the study due to exacerbation of seizures. Three patients were discontinued from the study for adverse events judged to be unrelated to study drug. Low incidences of rash (3.4%) and weight gain (0.8%) were reported. In this population of adults with seizure disorders, CBZ-ERC twice daily was well tolerated during 12 to 36 months of open-label treatment,with no increase in seizure frequency or decrease in quality of life.
    Clinical Therapeutics 11/2003; 25(10):2586-96. · 2.23 Impact Factor
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    ABSTRACT: Carbamazepine (CBZ) effectively treats simple, complex, and secondarily generalized partial seizures. Computer simulations were carried out to investigate the effect of missing or delaying doses of carbamazepine extended-release capsules (CBZ-ERC) on plasma CBZ levels and the optimal dosing strategy to return plasma concentrations to therapeutic levels. A one-compartment open model with first-order absorption and elimination was generated from the results of a previous study measuring plasma concentrations following one 400-mg fasting dose of CBZ-ERC. The model was used to simulate plasma CBZ concentrations following multiple doses given every 12 h to hypothetical long-term CBZ-treated patients, with the CBZ elimination half-life set to 13.7 h to account for enzymatic autoinduction. The model was then used to simulate plasma CBZ concentrations when a dose is taken 3, 6, or 9 h late, or when two doses are taken at one time. Predicted plasma CBZ concentrations in this simulation fell from a trough of approximately 6.4 microg/ml only to 4 microg/ml after 24 h without medication, and only to 2.5 microg/ml after 36 h without medication. Predicted plasma CBZ concentrations in this simulation never rose above 9 microg/ml, indicating that taking missed doses of CBZ-ERC as soon as remembered, up to two missed doses 3 h before taking the next scheduled dose, will not lead to harmful spikes in plasma concentrations of CBZ. The simulations suggest that taking a missed dose of CBZ-ERC as soon as remembered, up to two doses at one time, may be the best strategy to return plasma CBZ concentrations to steady-state levels. Since the model used in this study is a simplified model of a highly complex situation, caution should be used when relating these results to clinical practice until trials are conducted in patients.
    Current Medical Research and Opinion 02/2003; 19(6):519-25. · 2.37 Impact Factor
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    ABSTRACT: Phenytoin is the most commonly administered antiepileptic agent for the prevention of early (< or = 7 days) posttraumatic seizures. Use of the agent, however, requires strict monitoring due to its narrow target range and nonlinear pharmacokinetics. The impact of a clinical pharmacist participating in the care of patients with head injury on posttraumatic seizure prophylaxis with regard to phenytoin dosing and monitoring, cost avoidance, and patient outcome, was measured retrospectively. Parameters from time periods before (BP) and after (AP) a clinical pharmacist participated in patient care were compared. The average number of days that phenytoin was given was 13.4 (BP) and 7.6 (AP), and the duration of phenytoin prophylaxis was 7 days or less in 35% and 65% of patients, respectively. The average number of phenytoin levels drawn from each patient was 10.3 (BP) and 3.4 (AP). Seizures occurred in 4.7% (BP) and 1.5% (AP) of patients. A cost savings of approximately $28,000 was observed for the AP group. A clinical pharmacist reduced the use of posttraumatic seizure prophylaxis and associated costs without jeopardizing patient outcomes.
    Pharmacotherapy 03/2002; 22(2):251-5. · 2.31 Impact Factor
  • W R Garnett
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    ABSTRACT: Nonsteroidal antiinflammatory drugs (NSAIDs) often are prescribed to patients who are taking concomitant drugs. Cyclooxygenase (COX)-2 inhibitors (coxibs) rofecoxib and celecoxib are highly selective inhibitors of COX-2, differentiating them from nonselective NSAIDs, which substantially inhibit both COX-1 and COX-2. Like nonselective NSAIDs, coxibs are hepatically metabolized: rofecoxib primarily by reduction by cytosolic enzymes and celecoxib by the cytochrome P450 (CYP) enzyme system. Because rofecoxib is not significantly metabolized by CYP, it has fewer confirmed or potential drug interactions than celecoxib. However, potent inducers of CYP, such as rifampin, may decrease rofecoxib concentrations because of induction of general hepatic metabolic activity. Celecoxib is metabolized by CYP2C9 and may be increased or decreased by CYP2C9 modifiers. It also inhibits CYP2D6 and may affect concentrations of CYP2D6 substrates. Similar to NSAIDs, many pharmacodynamic interactions involving coxibs are related to inhibition of production of renal prostaglandins. However, coxibs have no antiplatelet activity and may be preferred to NSAIDs in patients receiving antithrombotic therapy. Nonetheless, when a potential for an interaction exists, standard monitoring is recommended when starting or discontinuing a coxib. Due to lack of data to support these interactions, which are primarily theoretical, additional studies are necessary to establish the drug interaction profiles of coxibs.
    Pharmacotherapy 11/2001; 21(10):1223-32. · 2.31 Impact Factor
  • W R Garnett, N Yunker
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    ABSTRACT: The role of infliximab in managing Crohn's disease (CD) is described. CD is characterized by chronic transmural inflammation at various sites of the gastrointestinal tract, particularly the ileum and colon. The major symptoms are diarrhea, abdominal pain, enterocutaneous and perianal fistulas, and weight loss. Management goals include alleviating symptoms, inducing remission, promoting healing of the intestinal mucosa and fistulas, and modifying the disease process. Drugs traditionally used to manage CD are aminosalicylates, antimicrobials, immunomodulatory agents, and corticosteroids. Infliximab is a chimeric (human-mouse) monoclonal antibody targeted at human tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine important in the pathogenesis of CD. Infliximab antagonizes the biological activity of TNF-alpha by binding to it on macrophage and T-cell surfaces. Clinical trials have shown infliximab to be effective in producing and maintaining a clinical response in patients with refractory, moderate to severe CD. Treatment helps promote healing of intestinal mucosa and closure of fistulas. Infliximab may act more rapidly than most traditional agents and produces less severe adverse effects. The most frequent adverse effects are headache, nausea, and upper-respiratory-tract infections. The recommended dosage is 5 mg/kg i.v. infused over a two-hour period. Infliximab may be given at eight-week intervals for maintenance or management of flare-ups. Infliximab appears useful in the treatment of CD and may improve patients' quality of life.
    American Journal of Health-System Pharmacy 03/2001; 58(4):307-16; quiz 317-9. · 1.98 Impact Factor
  • W R Garnett
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    ABSTRACT: The goal in treating patients with epilepsy is a cost-effective approach to the elimination of seizures or a reduction in their number and frequency while avoiding drug interactions and side effects, so as to achieve the best possible quality of life. Among the desirable outcomes are an enhanced understanding of epilepsy by patients, caregivers, and society, and a lessening of the psychosocial risks of this disease. Patients fail to achieve their goals and outcomes when they fail to adhere to the drug regimen or when a less-than-adequate drug regimen is prescribed. To help improve adherence, once- or twice-daily formulations should be used. New antiepileptic drugs (AEDs) increase the possibility of effective treatment for a patient who initially fails therapy. Working together, patients and clinicians can maximize the effectiveness of AED therapy and the potential for achieving desired goals and outcomes.
    Pharmacotherapy 09/2000; 20(8 Pt 2):191S-199S. · 2.31 Impact Factor
  • W R Garnett
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    ABSTRACT: Clinical success with an antiepileptic drug (AED) depends primarily on its efficacy and tolerability. Clinicians also need to have a basic understanding of an AED's pharmacokinetic characteristics, particularly those affecting the potential for drug interactions such as hepatic enzyme inhibition or induction and protein-binding displacement. Successful treatment may be complicated by pharmacokinetic characteristics such as a short half-life, nonlinear kinetics, and active metabolites. Pharmacokinetic characteristics that make a drug easy to use may affect patient adherence. In general, newer AEDs such as topiramate (TPM) are simpler to use than traditional AEDs because they have more favorable pharmacokinetic characteristics and fewer drug interactions.
    Epilepsia 02/2000; 41 Suppl 1:S61-5. · 3.91 Impact Factor
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    ABSTRACT: To determine the effects of the maximum recommended over-the-counter (OTC) cimetidine dosage on phenytoin concentrations in ambulatory seizure patients on long-term phenytoin therapy. Adults with seizure disorders requiring phenytoin therapy were recruited. Trough total phenytoin concentrations were measured initially and once weekly for six weeks. All assays were performed using Biotrack patient-side cartridges. After a two-week baseline period, patients took cimetidine 200 mg twice daily for two weeks. Toxicity was monitored via weekly neurologic examinations and midweek telephone surveys. Patients were asked to return to clinic weekly during a two-week cimetidine washout period. Nine patients entered and completed the study. All but two patients took other anticonvulsants known to interact with phenytoin (carbamazepine, n = 5; phenobarbital, n = 2). No adverse effects or changes in seizure frequency were reported. Paired Student's t-tests revealed no significant difference between serum phenytoin concentrations before (12.3+/-3.2 mg/L [mean +/- SD]) and after (12.8+/-4.0 mg/L) two weeks on the OTC cimetidine regimen. No differences were noted in estimated pharmacokinetic parameters (maximum metabolic rate, Michaelis-Menten constant) for the same time periods (paired Student's t-test, p > 0.05). The Biotrack assay had an r2 = 0.7311 (p < 0.001, two-sided) when compared with TDx. It is possible that the lack of change in phenytoin concentrations was a result of the low daily dosage of cimetidine used or other factors related to the "real world" setting of the study. However, the potential for a serious drug interaction occurring in patients taking long-term oral phenytoin and OTC cimetidine appears to be small.
    Annals of Pharmacotherapy 01/1999; 33(7-8):769-74. · 2.57 Impact Factor
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    ABSTRACT: We evaluated the use of a new, controlled-release capsule form of carbamazepine, Carbatrol capsules, in an open-label, multicenter study of 124 patients with complex partial seizures. Ninety-one percent of the patients successfully completed the 6-month trial with good seizure control, with a significant improvement in quality of life. We conclude that switching patients with complex partial seizures from multiple daily-dose carbamazepine to twice-daily Carbatrol on a milligram-to-milligram basis is relatively safe.
    Neurology 01/1999; 51(6):1727-9. · 8.25 Impact Factor

Publication Stats

560 Citations
168.82 Total Impact Points

Institutions

  • 1986–2011
    • Virginia Commonwealth University
      • • School of Pharmacy
      • • Department of Pharmaceutics
      • • Medical College of Virginia Campus
      Richmond, VA, United States
  • 1999
    • The School of Pharmacy
      • School of Pharmacy
      Fort William, Scotland, United Kingdom
  • 1989
    • Research Triangle Park Laboratories, Inc.
      Raleigh, North Carolina, United States
    • Richmond Hospital
      Richmond, British Columbia, Canada
    • Julphar School of Pharmacy
      Richmond, Virginia, United States