Bioequivalence of Carbamazepine Chewable and Conventional Tablets: Single-Dose and Steady-State Studies

Chan, Keith; Sawchuk, Ronald J.; Thompson, Thomas A.; Redalieu, Elliot; Wagner, William E.; Lesher, A.R.; Weeks, B.J.; Hall, Nancy; Gérardin, A.

doi:10.1002/jps.2600740813

Cited by 20 publications

(8 citation statements)

References 16 publications

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“…In a chronic dose study of healthy volunteers Chan et al (1985) observed that the mean Cma of CBZ was 7% higher during CBZ-CHEW administration compared to CBZ-C. In the present study with epileptic patients we were unable to confirm those results.…”

Section: Dsussionscontrasting

confidence: 86%

A comparative pharmacokinetic study of conventional and chewable carbamazepine in epileptic patients.

Patsalos

1990

Brit J Clinical Pharma

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Using an open substitution study design, conventional carbamazepine (Tegretol, CBZ‐C and a chewable carbamazepine formulation (Tegretol Chewtabs, CBZ‐CHEW) were compared in 12 patients with severe intractable epilepsy. During a dosing interval, no significant differences were observed with respect to trough or peak serum concentrations of CBZ and CBZ‐10,11‐epoxide (CBZ‐E), the active metabolite. The area under the serum CBZ concentration‐time curve for a dosing interval was (mean +/− s.e. mean) 146 +/− 10 mumols l‐1 h on CBZ‐ C and 143 +/− 9 mumols l‐1 h on CBZ‐CHEW. The two formulations, therefore, have a similar pharmacokinetic profile and could be used interchangeably in the management of patients with epilepsy.

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Section: Dsussionscontrasting

confidence: 86%

A comparative pharmacokinetic study of conventional and chewable carbamazepine in epileptic patients.

Patsalos

1990

Brit J Clinical Pharma

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“…The rate of carbamazepine absorption is relatively slow, variable, and formulation dependent. The time required to reach peak serum concentrations (T max ) following single oral doses of immediate‐release tablets, chewable tablets, and suspension is in the range of 2–9 h, 1–7 and 0.5–4 h, respectively (Chan et al, 1985; Graves et al, 1985; Maas et al, 1987; Patsalos, 1990a). The bioavailability of carbamazepine is 75–85%, although the lack of an injectable formulation precludes precise determination of the exact value.…”

Section: Relevance Of Tdm For Individual Aedsmentioning

confidence: 99%

Antiepileptic drugs—best practice guidelines for therapeutic drug monitoring: A position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies

et al. 2008

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SUMMARYAlthough no randomized studies have demonstrated a positive impact of therapeutic drug monitoring (TDM) on clinical outcome in epilepsy, evidence from nonrandomized studies and everyday clinical experience does indicate that measuring serum concentrations of old and new generation antiepileptic drugs (AEDs) can have a valuable role in guiding patient management provided that concentrations are measured with a clear indication and are interpreted critically, taking into account the whole clinical context. Situations in which AED measurements are most likely to be of benefit include (1) when a person has attained the desired clinical outcome, to establish an individual therapeutic concentration which can be used at subsequent times to assess potential causes for a change in drug response; (2) as an aid in the diagnosis of clinical toxicity; (3) to assess compliance, particularly in patients with uncontrolled seizures or breakthrough seizures; (4) to guide dosage adjustment in situations associated with increased pharmacokinetic variability (e.g., children, the elderly, patients with associated diseases, drug formulation changes); (5) when a potentially important pharmacokinetic change is anticipated (e.g., in pregnancy, or when an interacting drug is added or removed); (6) to guide dose adjustments for AEDs with dose-dependent pharmacokinetics, particularly phenytoin.

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“…This 'intrinsic crossover' design has the following advantages over the conventional cross-over design; a) The problem of intra-subject variability between different study days is avoided. b) The study can be performed over a shorter period of time, a particular advantage for a compound such as CBZ which has a long terminal plasma elimination half-life (approximately 35 h after a single dose; Chan et al, 1985). Hence plasma drug concentrations have to be followed for at least 7 days postdosing to characterise fully the profile.…”

Section: Introductionmentioning

confidence: 99%

Relationship between systemic drug absorption and gastrointestinal transit after the simultaneous oral administration of carbamazepine as a controlled‐release system and as a suspension of 15N‐labelled drug to healthy volunteers.

Wilding

Davis

Hardy

et al. 1991

Brit J Clinical Pharma

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1. Plasma drug concentrations after a single oral administration of a suspension of carbamazepine (CBZ) and a 20/200 CBZ Oros osmotic pump system were measured in eight healthy male volunteers. The oral suspension contained 100 mg CBZ labelled with the stable isotope nitrogen‐15, whilst the Oros contained 200 mg unlabelled CBZ. Plasma concentrations of [15N]‐CBZ and CBZ were measured simultaneously by gas chromatography‐mass spectrometry. 2. The position of the CBZ Oros (labelled with indium‐111) in the gastrointestinal tract was followed by gamma scintigraphy. Plasma drug concentrations after the two treatments were used to relate pharmacokinetic with transit data. 3. The Oros was taken after breakfast and gastric emptying occurred between 1.1‐ greater than h post‐dosing (median, 5.3 h). Small intestinal transit times ranged from 1.5‐ greater than 3.6 h, with a median of 2.2 h. There were wide individual variations in colonic transit, and the total transit time ranged from 10‐60 h (median, 22 h). 4. Relative systemic bioavailability of CBZ from the Oros was reduced compared with that from the suspension (mean dose normalised AUC ratio = 0.69 +/‐ 0.17; mean dose‐normalised AUC ratio = 0.85 +/‐ 0.13, allowing for actual release from the Oros system). 5. The in vivo absorption of drug into the systemic circulation from the Oros was estimated using the Wagner‐Nelson method. This showed that absorption of CBZ was rapid when the Oros was present in the stomach and small intestine, the rate being determined by the release of drug from the system.(ABSTRACT TRUNCATED AT 250 WORDS)

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Bioequivalence of Carbamazepine Chewable and Conventional Tablets: Single-Dose and Steady-State Studies

Cited by 20 publications

References 16 publications

A comparative pharmacokinetic study of conventional and chewable carbamazepine in epileptic patients.

A comparative pharmacokinetic study of conventional and chewable carbamazepine in epileptic patients.

Antiepileptic drugs—best practice guidelines for therapeutic drug monitoring: A position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies

Relationship between systemic drug absorption and gastrointestinal transit after the simultaneous oral administration of carbamazepine as a controlled‐release system and as a suspension of 15N‐labelled drug to healthy volunteers.

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