Effect of Piperine on the Metabolism and Pharmacokinetics of Carbamazepine in Healthy Volunteers.

Carbamazepine (CBZ) is a widely used antiepileptic drug with narrow therapeutic window and it may be prone to drug interactions. The purpose of present study was to investigate the effect of PIP on metabolism and pharmacokinetics of CBZ in healthy volunteers. An open-label, 2 period, sequential study was conducted in 12 healthy volunteers. PIP 20 mg was administered once daily for 10 days during treatment phase. A single dose of CBZ 200 mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected after CBZ dosing at predetermined time intervals and analyzed by LC-MS/MS method. Treatment with PIP significantly enhanced maximum plasma concentration (Cmax), area under the curve (AUC) and half life (T1/2) of CBZ by 68.7, 47.9 and 43.2%, respectively as compared to control. On the other hand, elimination rate constant (Kel) and apparent oral clearance (CL/F) of CBZ were significantly decreased by 23.8 and 38.9%, respectively upon PIP treatment as compared to control. Furthermore, PIP treatment significantly decreased metabolic (CBZE/CBZ) ratios of Cmax and AUC, indicating the decreased formation of CBZ to CBZE. The results suggest that the altered CYP3A4 enzyme activity and pharmacokinetics of CBZ might be attributed to PIP mediated inhibition of CYP3A4 enzyme. Thus, there is a potential pharmacokinetic interaction present between PIP and CBZ. Accordingly, caution should be taken when PIP is used in combination with therapeutic drugs metabolized by CYP3A4 in addition to CBZ.

Nitric oxide metabolites in sera of patients across the spectrum of leprosy.

Leprosy, a chronic infectious disease, caused by Mycobacterium leprae infection, manifests itself as a clinical spectrum depending on the patients' immunological response, finally leading to peripheral nerve damage and deformities in the patients. Nitric oxide (NO) which is known to contribute to pathogenesis of several neurological diseases has been detected in tissues and urine of leprosy patients. This is the first study assessing NO as its stable end products, nitrites and nitrates, in sera of patients across the spectrum of the disease as a possible parameter of prognostic value. Comparison of NO metabolites showed a significant increase in multibacillary patients and patients with type I reactions as compared to healthy control individuals. These levels reduced significantly after treatment. This study has further borne out the utility and reliability of the cadmium-reduction method of estimation of NO metabolites--a relatively inexpensive procedure that lends itself to large-scale screening and follow-up of patients.

[Peri-acetabular pelvic osteotomy in the treatment of congenital hip dislocation in older children and adolescents]. / L'ostéotomie pelvico péri-acétabulaire dans le traitement de la luxation congénitale de la hanche du grand enfant et de l'adolescent.

The author describes a double osteotomy combining a pelvic (Salter) type of osteotomy and a periacetabular (Pemberton) type of osteotomy performed in one procedure by an anterior approach and aimed at a re-orientation of the acetabulum and a correction of any dysplasia. The technique is indicated in older children and adolescents when other procedures are not possible. However, this operation is not possible in cases where the circumference of the upper part of the acetabulum is smaller than that of the femoral head. It was applied in 30 hips with satisfactory results after a mean follow-up of one year.