Effect of diclofenac alone or in combination with alpha-tocopherol on the oxidative activity of polymorphonuclear leukocytes in healthy and osteoarthritic individuals

To investigate the effects of diclofenac alone or when combined with alpha-tocopherol on the oxidative activity of polymorphonuclear leukocytes [PMNs] in healthy and osteoarthritic [OA] patients. The study was carried out at the College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia, over the period 1999 to 2000. Twelve healthy controls and 12 osteoarthritic patients were recruited to the study. Twelve healthy controls and osteoarthritic patients were given diclofenac 50 mg thrice daily orally, initially for 5 days then alpha-tocopherol at 200 mg thrice daily orally, was added for another 5 days. Blood samples were drawn before the start of the study [pre-treatment] and at 5 days following treatment with diclofenac alone and 10 days following treatment with diclofenac and alpha-tocopherol. Chemiluminescence [CL] response was measured for whole blood and isolated polymorphonuclear leukocytes [PMNs] on all samples. Diclofenac enhanced CL response of whole blood and of PMNs of healthy controls when stimulated with phorbol myristate acetate [PMA] and opsonized zymosan [OPZ]. Co-treatment with alpha-tocopherol resulted in no appreciable change in the CL response of whole blood when stimulated with PMA or OPZ but a further significant enhancement of CL response of isolated PMNs when these cells were stimulated by either PMA or OPZ. In osteoarthritic patients, diclofenac alone and when combined with alpha-tocopherol showed no significant change in CL response of whole blood. The CL response of PMNs from OA patients was decreased by diclofenac alone. However, this inhibitory effect was not observed when alpha-tocopherol was used together with diclofenac. The effect of diclofenac alone or in combination with alpha-tocopherol did not produce a consistent effect on the CL response of whole blood or isolated PMNs of healthy or osteoarthritic patients

Effect of pregnancy on the pharmacokinetics of lamotrigine in rabbits

The effect of pregnancy on the pharmacokinetic profile of orally administered doses of lamotrigine was investigated in the rabbit. Pregnant rabbits were given lamotrigine [20 mg/kg, p.o.] daily for one week starting on day 19 of gestation. Similarly, non-pregnant rabbits received the same oral doses of lamotrigine for the same period. Plasma lamotrigine levels were monitored over a 24 h period using a high-performance liquid chromatographic [HPLC] method. Administration of lamotrigine to pregnant rabbits resulted in a significant increase [p < 0.05] in the maximum plasma concentration C[max] and the mean area under the plasma concentration - time curve [AUC] and a significant decrease [p<0.05] in total body clearance [CL/F] and volume of distribution at steady state [V d[ss]/F] as compared to those obtained for lamotrigine given to non-pregnant rabbits. No significant changes were observed in the mean time to reach maximum concentration T[max] and the elimination half-lives t[1/2] of lamotrigine between pregnant and non-pregnant rabbits. Our data suggest that the plasma concentrations of lamotrigine tended to be higher in pregnant than in non-pregnant rabbits. These findings may emphasize the importance of monitoring the plasma concentrations of lamotrigine during pregnancy and dose adjustments made as needed