Pharmacokinetics of S-Adenosylmethionine Delivered in Enteric Coated Tablets to Healthy Cats: Acute & Chronic Oral Dosing Study
WSAVA 2002 Congress
*SA Center, KL Warner
*College of Veterinary Medicine, Cornell University
Ithaca, New York, US
sac6@cornell.edu

OBJECTIVES

To evaluate acute and chronic pharmacokinetics profiles of orally administered SAMe in healthy cats given enteric coated tablets containing s-adenosylmethionine (SAMe) as the stabilized 1,4-butanedisulfonate salt (Denosyl-SD4; Nutramax Laboratories, Inc., Edgewood, New Jersey, USA).

MATERIALS

Intact female cats (n=15), mean (std dev)age of 4.5 (1.4) yrs, body weight of 3.45 (0.59) kg, health status determined by physical examination, routine hematologic, serum biochemical, and urine analyses, were orally administered SAMe for 118 days. A mean dose of 53.8 (7.7) mg/kg was given after a 12-hr fast with food withheld an additional 4-hrs. Pharmacokinetics were determined on days 0, 24, and 118. Blood was collected into heparin vacutainers before and 2, 4, 8, and 12 hrs after dosing. Plasma was immediately separated and stored frozen at -80°C until SAMe analyses by high pressure liquid chromatography (HPLC)as described by Lieber et al.1 On-line purification/pre-concentration of SAMe with a cation exchange precolumn preceded elution onto a reversed-phase analytical HPLC column. Intra- and inter-assay repeatability were determined using 3 batches of plasma assayed 5 times each, at baseline and spiked with 32, 893, and 2,300 ng/ml SAMe. Recovery (%) of samples "spiked" with SAMe was determined using a pooled basal plasma sample to which 29, 143, and 1,430 ng/ml SAMe was added; each sample assayed 5 times. Data was analyzed for differences in hourly SAMe concentrations and cumulative concentration (area under the curve, AUC) between days.

RESULTS

Intra- and inter-assay repeatabilities yielded CV% < 5.0% and < 15%, respectively. Recovery of SAMe from baseline samples spiked with 29, 143, and 1,430 ng/ml were 99.6 %, 97.8%, and 101.0%, respectively. Mean plasma SAMe concentrations (ng/ml) on Days 0, 28, and 118, were as follows; Baseline: 39.4 +/- 10.6, 109.6 +/- 31.4, and 102.3 +/- 44.4; 2 hrs: 1,432.4 +/- 269.6, 710.5 +/- 194.3, and 1,600.9 +/- 215.6; 4 hrs: 1,482.2 +/- 283.6, 1,411.1 +/- 367.2, and 1,692.6 +/- 220.9; 8 hrs: 895.1 +/- 158.4, 858.7 +/- 158.4, and 606.3 +/-152.3; and 12 hrs: 472.7 +/-139.4, 474.5 +/- 160.4, and 349.4 +/- 95.7, respectively. The AUC was 11,877 +/- 9,356 for day 0, 10,147 +/- 6,117 for Day 28, and 11,506 +/- 5,813 for day 118. Significantly greater plasma SAMe concentrations developed at all post-dosing intervals compared to baseline; p < 0.05. There were no significant differences in AUC.

CONCLUSION

Healthy cats absorb the stable 1,4-butanedisulfonate salt form of SAMe from enteric coated tablets achieving significantly increased plasma concentrations at post-dosing intervals through 12 hours. Peak plasma concentrations develop at 2 to 4 hours. Chronic administration did not significantly alter plasma SAMe concentrations.

References

1.  Lieber CS, Casini A, DeCarli LM,, et al: S-adenosyl-L-methionine attenuates alcohol-induced liver injury in the baboon. Hepatology 1990;11:165-172.

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

S A Center
Cornell University
College of Veterinary Medicine
Ithaca, NY 14853 USA

K L Warner
College of Veterinary Medicine, Cornell University


MAIN : : S-Adenosylmethionine Enteric Coated Tablets
Powered By VIN
SAID=27