When the plasma glutathione concentration is low, such as in patients with HIV infection, alcoholics, and patients with cirrhosis, increasing the availability of circulating glutathione by oral administration might be of therapeutic benefit. To assess the feasibility of supplementing oral glutathione we have determined the systemic availability of glutathione in 7 healthy volunteers. The basal concentrations of glutathione, cysteine, and glutamate in plasma were 6.2, 8.3, and 54 mumol.l-1 respectively. During the 270 min after the administration of glutathione in a dose of 0.15 mmol.kg-1 the concentrations of glutathione, cysteine, and glutamate in plasma did not increase significantly, suggesting that the systemic availability of glutathione is negligible in man. Because of hydrolysis of glutathione by intestinal and hepatic gamma-glutamyltransferase, dietary glutathione is not a major determinant of circulating glutathione, and it is not possible to increase circulating glutathione to a clinically beneficial extent by the oral administration of a single dose of 3 g of glutathione.

BACKGROUND/AIMS Exenatide, a novel therapy for type 2 diabetes, among other glucoregulatory actions, slows gastric emptying and may alter the rate of absorption of concomitant oral drugs. As statins are commonly used in patients with type 2 diabetes, the potential interaction between exenatide and statins was evaluated. METHODS [A] PK study: open‐label, fixed‐sequence study in 21 healthy subjects. Lovastatin PK was evaluated after a single dose of lovastatin (40 mg) administered alone and in combination with concomitant exenatide (10 μg BID). [B] Long‐term clinical trials: Data from statin users in three 30‐week, placebo‐controlled trials for exenatide were combined and stratified based on concomitant placebo (n=168) or exenatide (n=180) use. Lipid profiles and statin dosage were compared between the active and placebo arms. RESULTS [A] PK study: Exenatide decreased mean lovastatin Cmax and AUC 0‐∞ by 28% and 40% respectively and increased median tmax by about 4 hours. [B] Long‐term trials: Changes for fasting HDL‐C, LDL‐C, total cholesterol, triglycerides and the subjects (6 total) that increased their statin dose were not significantly different between the exenatide and placebo groups (see table). CONCLUSIONS Despite changes in lovastatin PK observed in an acute study, long‐term exenatide treatment did not alter HDL‐C, LDL‐C, total cholesterol, or triglycerides or require increases in statin dose. These data indicate that no change in statin dose is required during use with exenatide. LS mean±SE change from baseline to week‐30 Placebo LS mean±SE change from baseline to week‐30 Exenatide LS mean±SE of difference between treatments (95% CI) p‐value for the difference HDL‐C (mg/dL)1.7 ± 0.61.1 ± 0.6−0.6 ± 0.7(−2.1, 0.8)0.4052LDL‐C (mg/dL)3.1 ± 2.71.7 ± 2.6−1.5 ± 3.4(−8.1, 5.2)0.6668Cholesterol (mg/dL)5.3 ± 3.01.4 ± 2.9−3.9 ± 3.8(−11.3, 3.5)0.3009Triglycerides (mg/dL)5.3 ± 13.4−23.6 ± 12.9−29.0 ± 16.7(−61.9, 3.9)0.084Patients who increased statin dosage (%)2.41.1‐0.4347 Clinical Pharmacology & Therapeutics (2005) 79, P46–P46; doi:

Background: Alzheimer’s disease is a progressive neurodegenerative disorder characterized by cognitive deterioration together with declining activities of daily living and behavioural changes. The present work is aimed to investigate the effect of methanolic extract of rhizomes of Picrorhiza kurroa against aluminum chloride induced Alzheimer’s disease.Methods: Wistar rats were selected in this study and were divided into 5 groups (6 each). Group I served as normal control. Group II received aluminum chloride (300mg/kg, P.O.). Group III and IV received ethanolic extract of Picrorhiza kurroa (200mg/kg, 400mg/kg, P.O. respectively) and inducing agent (AlCl3 300mg/kg, P.O.). Group V received rivastigmine (0.3mg/kg, I.P.) and inducing agent (AlCl3 300mg/kg, P.O.). The rats were given respective treatment for 20 days and behavioural parameters were determined on 20th day. After 20th day rats were sacrificed and anti-oxidant parameters, brain acetylcholinesterase content were determined.Results: Oral administration of ethanolic extract of Picrorhiza kurroa at doses 200, 400mg/kg body weight showed improve in behavioural parameters when compared to AlCl3 induced rats, showed increase in superoxide dismutase, catalase, reduced glutathione and decreased levels of malondialdehyde and showed decrease in brain acetylcholinesterase content when compared to AlCl3 induced rats.Conclusions: The study clearly demonstrated the beneficial effects of Picrorhiza kurroa by improving biochemical and behavioural parameters.