Rectal absorption of lamotrigine compressed tablets.
OBJECTIVE
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 single-dose, 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 microg/mL/hr after rectal administration and 51.71 +/- 19.2 microg/mL/hr after oral administration. The average maximum LTG concentration was 0.53 +/- 0.14 microg/mL after rectal administration and 1.45 +/- 0.35 microg/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.
Birnbaum
A K
AK
Experimental and Clinical Pharmacology and Medicinal Chemistry, Epilepsy Research and Education Program, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA. birnb002@tc.umn.edu
Kriel
R L
RL
Burkhardt
R T
RT
Remmel
R P
RP
D000284:Administration, Oral; D000285:Administration, Rectal; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D007408:Intestinal Absorption; D000077213:Lamotrigine; D012007:Rectum / Q000378:metabolism; D016037:Single-Blind Method; D014227:Triazines / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine