Evaluation of the effect of ammonia on nicotine pharmacokinetics using rapid arterial sampling.

Introduction: 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.

Diazepam autoinjector intramuscular delivery system versus diazepam rectal gel: A pharmacokinetic comparison.

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.

Rapid automated blood sampling system for pharmacokinetics studies of cigarette smoking.

Introduction: 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.

Methods: Components of the system include silastic tubing, solenoid pinch valves, a peristaltic pump, and a fraction collector.

Transitional polytherapy: tricks of the trade for monotherapy to monotherapy AED conversions.

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.

Conversions between monotherapies in epilepsy: expert consensus.

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.

The use of Monte Carlo simulations to study the effect of poor compliance on the steady state concentrations of valproic acid following administration of enteric-coated and extended release divalproex sodium formulations.

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.

Carbamazepine extended-release capsules vs. oxcarbazepine: computer simulations of the effect of missed doses on drug plasma concentrations.

Objective: 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).

Optimizing antiepileptic drug therapy in the elderly.

Objective: To review and evaluate the medical literature concerning antiepileptic drug (AED) therapy in elderly patients.

Data Sources: 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.

Patterns of care, outcomes, and direct health plan costs of antiepileptic therapy: a pharmacoeconomic analysis of the available carbamazepine formulations.

Background: 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.

Objective: 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]).

Carbamazepine pharmacokinetics are not affected by zonisamide: in vitro mechanistic study and in vivo clinical study in epileptic patients.

Carbamazepine is metabolized by CYP3A4 and several other cytochrome P450 enzymes. The potential effects of zonisamide on carbamazepine pharmacokinetics (PK) have not been well characterized, with contradictory literature reports. Hence, an in vitro study was designed to evaluate the cytochrome P450 inhibition spectrum of zonisamide using human liver microsomes.

Lack of a clinically significant effect of zonisamide on phenytoin steady-state pharmacokinetics in patients with epilepsy.

This study was designed to measure the effect of the addition of zonisamide on phenytoin pharmacokinetics under steady-state conditions in patients with epilepsy. Nineteen patients stabilized under phenytoin monotherapy were included in a 3-center, open-label, 1-way drug interaction trial. Zonisamide was gradually increased to 400 mg/day, taken twice daily.

Tolerability and effects on quality of life of twice-daily extended-release carbamazepine in adults with seizure disorders: an open-label, 12- to 36-month continuation study.

Background: 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).

Objective: 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.

Simulation of the effect of patient nonadherence on plasma concentrations of carbamazepine from twice-daily extended-release capsules.

Objective: 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.

Patients And Methods: 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.

History of acid suppression: focus on the hospital setting.

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.

Pharmacist impact on posttraumatic seizure prophylaxis in patients with head injury.

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.

Disposition of Misoprostol and Its Active Metabolite in Impaired Hepatic Function.

The pharmacokinetics of misoprostol and its active metabolite, misoprostol acid, was assessed in 17 healthy subjects and 17 subjects with various degrees of hepatic impairment. Before misoprostol administration, subjects underwent antipyrine and indocyanine green clearance studies to assess hepatic functional capacity. Subjects were administered 400 mcg of oral misoprostol in an open-label design.