Rectal Absorption of Lamotrigine Compressed Tablets

Abstract

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...

Relative Bioavailability of Lamotrigine Chewable Dispersible Tablets Administered Rectally

“…A similarly designed study conducted in this laboratory with a compressed LTG tablet yielded relative bioavailability of 0.63 ± 0.33. 15 In the current study, relative bioavailability after rectal administration of the chewable dispersible tablet was 0.52 ± 23. Rectal absorption was lower after administration of this suspension compared with oral absorption of the intact tablet.…”

Status Epilepticus: A Review of Different Syndromes, Their Current Evaluation, and Treatment

“…Because many AEDs do not have parenteral preparations, this presents a challenge for patients with ileus or other gastrointestinal problems. Some maintenance medications, including carbamazepine and lamotrigine, demonstrate lower but sufficient bioavailability when given rectally versus orally (119,120). Gabapentin and oxcarbazepine do not have adequate rectal absorption (121,122).…”

Intramuscular and rectal therapies of acute seizures

“…The relative bioavailability for LTG compressed tablets was 0.63 ± 0.33 and the T max was 6.54 ± 2.90 h [75].…”