Absorption of valproic acid from the gastrointestinal tract of the piglet

Abstract

Valproic acid is a commonly used drug for the treatment of epilepsy. Since valproic acid can only be given orally, its absorption from the gastrointestinal (GI) tract especially in patients with short bowel syndrome (SBS) and in neonates is important. The specific sites of absorption for valproic acid in the small intestine and colon have not been investigated. It is currently unknown whether these patients are able to absorb oral valproic acid sufficiently to maintain a therapeutic serum concentration. The primary objectives of the study were to: (a) determine the relative absorption of valproic acid from specific sites in the GI tract; and (b) investigate the influence of intestinal development on valproic acid absorption using the newborn piglet as a model. Two groups were studied: Group I included 5 piglets 18-21 days of age, and Group II included 5 piglets 1-3 days of age. A valproic acid solution was simultaneously perfused through 5 partitioned segments of the gastrointestinal tract: the duodenum, jejunum, ileum, right colon and left colon. Tritiated [3H] polyethylene glycol was co-administered to monitor water movement across the GI mucosa. Following steady state, samples were collected from each segment, and analyzed by a specific enzyme-mediated immunoassay. The absorption rates (micrograms/min/cm) of valproic acid in Group I were as follows: 9.96 +/- 2.8 duodenum; 11.28 +/- 2.79, jejunum; 9.42 +/- 3.34, ileum; 10.88 +/- 3.35, right colon; 10.96 +/- 2.92, left colon.(ABSTRACT TRUNCATED AT 250 WORDS)

Successful Treatment of Symptomatic Epilepsy with Oral Valproic Acid and Levetiracetam in a Patient with Short-bowel Syndrome

“…We encountered a patient with short-bowel syndrome and a 30-cm residual small intestine who was administered VPA and LEV. According to studies on VPA in rats and pigs, the absorption of VPA from the stomach and duodenum to the colon is good ( 6 , 7 ); however, its gastrointestinal absorption in humans is unknown. Moreover, there have been no reports of VPA use in patients with short-bowel syndrome.…”

Absorption of theophylline from the small and large intestine of the neonatal piglet

“…The methods of preparation and in vivo perfusion of piglets were reported in detail previously (4,5). In brief, pentobarbital (Nembutal) anesthesia was employed at a dose of 35 mgIkg, intraperitoneally.…”

“…the combined dose in 4 segments was 5 mglkg). Polyethylene glycol (eHl-PEG 4000, 6 J.l.CiI1), a marker that is not absorbed during perfusions of the colon of newborns, was added to the perfusates to calculate water movement during perfusions (4,5). Each solution was perfused at a rate of 0.6 m.Vmin, over 60 min.…”

“…represents intravenous dosing. Theophylline, water, and sodium absorption from each segment was calculated as outlined in a previous report (5). Data were expressed as mean ± standard deviation (SO).…”

“…tracer technique was utilized to monitor the flux of water across the GI mucosa, by scintillation counting of eH]-PEG 4000 concentration in the effluent (model 2200cA, Liquid Scintillation Analyzer, Packard, Downer's Grove, IL, USA)(4,5). Osmolality was measured by freezing point depression (Advanced Micro-osmometer 3 MO, Advanced Instruments, Inc., Needham Heights, MA, USA).…”