Relative Bioavailability of Rectally Administered Carbamazepine Suspension in Humans

Graves, Nina M.; Kriel, Robert L.; Jones-Saete, Carolyn; Cloyd, James C.

doi:10.1111/j.1528-1157.1985.tb05675.x

Cited by 48 publications

(14 citation statements)

References 16 publications

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“…Rectal absorption of the drug from suppository or suspension has been observed by previous workers (Johannessen et al, 1984;Graves et al, 1985;Neuvonen & Tokola, 1987). Although the absorption was significantly slower via the rectal route, the total bioavailability was similar as long as the formation was not defaecated (Neuvonen & Tokola, 1987).…”

Section: Discussionmentioning

confidence: 50%

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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Section: Discussionmentioning

confidence: 50%

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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“…The rectal route of administration has been studied for several AEDs (valproate (l), carbamazepine (2) tained from each subject. Qualified subjects were asked to fill out a health questionnaire.…”

Section: Methodsmentioning

confidence: 99%

Rectal Absorption of Lamotrigine Compressed Tablets

Kriel

Burkhardt

2000

Epilepsia

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Summary:Purpose: Interruption of oral drug administration poses a significant clinical problem for antiepileptic drugs that have no parenteral formulation. If a drug is absorbed rectally, rectal administration can be a useful alternative when the oral route of administration is not possible. The purpose of this study was to compare the single-dose pharmacokinetics of lamotrigine (LTG) compressed tablets after rectal and oral administration in healthy volunteers.Methods: A single LTG compressed tablet (100 mg) was administered orally and rectally to 12 volunteers in this singledose, two-period, crossover study with a 2-week washout between doses. For rectal administration, tablets were crushed and suspended in 10 mL of water. Plasma samples were collected from 0 to 120 hr after each dose and analyzed for LTG by an HPLC method developed for this investigation.Results: LTG plasma concentrations were lower after rectal administration versus oral administration. The average area under the curve was 28.90 * 9.5 p,g/mL/hr after rectal administration and 51.71 f 19.2 pg/mL/hr after oral administration. The average maximum LTG concentration was 0.53 & 0.14 pg/mL after rectal administration and 1.45 +. 0.35 pg/mL after oral administration. The relative bioavailability for LTG compressed tablets was 0.63 & 0.33 for rectal administration. There were no drug-related rashes or serious side effects.Conclusions: LTG suspension prepared from LTG compressed tablets is absorbed rectally, although not to the same extent or rate as when given orally. Key Words: Lamotrigine-Rectal-Bioavailability-Compressed-Antiepileptic.Lamotrigine (LTG) is an antiepileptic drug (AED) approved for use in adults with partial seizures and in pediatrics and adults for the treatment of generalized seizures of Lennox-Gastaut syndrome. Currently, LTG is available in two formulations: an oral compressed tablet (25, 100, 150, and 200 mg) and a chewable dispersible tablet (5 and 25 mg). No parenteral formulation is available; therefore LTG therapy cannot be continued when a patient is vomiting, undergoing surgery, or experiencing gastrointestinal illness. Interruption of LTG administration increases the risk of increased seizure activity during these episodes. Alternative routes of administration, including the rectal route, are needed to minimize seizure risk when patients cannot take LTG by mouth.hyde (7)). Some AEDs should not be given rectally because of poor solubility in aqueous solutions. For example, the relative bioavailabilities of gabapentin (8) and phenytoin (9) were low after rectal administration with current formulations, thus making them unsuitable for this route.The purpose of this study was to compare the singledose pharmacokinetics of LTG compressed tablets formulated as an aqueous suspension and administered rectally to the pharmacokinetics after oral administration of compressed tablets in healthy volunteers. METHODSThe rectal route of administration has been studied for several AEDs (valproate (l), carbamazepine (2), loraze- Study desig...

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“…Doses of approximately 6 mg/kg were given. There was no significant difference in total absorption, maximum serum concentration, and time to achieve maximum serum concentration (4 to 8 h) between the orally administered tablet and the rectally administered suspension [71]. Oral CBZ syrup was given per rectum using 400-mg equivalent aliquots to evaluate the potential use of rectal CBZ as alternative long-acting treatment following the termination of cluster seizures or status epilepticus.…”

Section: Hydantoins: Phenytoin and Fosphenytoinmentioning

confidence: 99%