Interactions of saquinavir with ketoconazole, erythromycin and rifampicin were observed in healthy volunteers as well as patients. The effects observed in patients, however, appear to be less pronounced. The enzyme induction caused by rifampicin might lead to subtherapeutic levels of saquinavir and this finding appears to be of clinical relevance.
It is now established that the overall prognosis for epilepsy is good and that remission will occur in at least 75% of patients following adequate treatment with monotherapy. Patients who fail to respond to monotherapy, who are not suitable for surgery, and who continue to have frequent seizures may have to be considered for an alternative drug regimen. A review of the literature indicates that complete seizure control with adjunctive treatment is rare, but improved seizure control can be obtained in up to 40% of patients. In a study of clobazam as adjunctive treatment, 60% (N = 20) of our patients responded to treatment initially and 33% maintained an improvement over an 18-month period. In 31 patients who failed to respond to carbamazepine as monotherapy, primidone (N = 16) or valproate (N = 15) were prescribed as adjunctive treatment. One patient obtained complete freedom from seizures and 14 (45%) had a greater than 50% reduction in seizure frequency. Suggested indications for the use of additive treatment in epilepsy are discussed.
An investigation of hypothalamic pituitary axis (HPA) function was performed on children and adolescents receiving long-term monotherapy with either carbamazepine (CBZ) or sodium valproate (NaV). There was a significant reduction in total T4 in the CBZ group. Free T4, T3, and thyroid-stimulating hormone response to thyrotropin-releasing hormone were similar in both groups. All patients produced an adequate growth hormone response to either arginine or L-Dopa. Basal cortisol levels were similar in both groups. An appropriately increased response in luteinising hormone, prolactin, testosterone, and oestradiol occurred in those after puberty. The results suggest that HPA function in children is not compromised by long-term monotherapy with CBZ or NaV.
Welwyn Garden City, UKAims To evaluate the potential pharmacokinetic interaction between the HIV protease inhibitor saquinavir and rifabutin. Methods Fourteen HIV-infected patients provided full steady-state pharmacokinetic profiles following administration of rifabutin alone (300 mg once daily) or saquinavir soft-gel formulation (1200 mg three times daily) plus rifabutin (300 mg once daily) in this open label, partially randomized study. Results Coadministration of saquinavir and rifabutin resulted in a reduction in saquinavir AUC(0,8 h) and C max (0,8 h) of 47% (95% CI 30, 60%) and 39% (95% CI 11, 59%), respectively. Rifabutin AUC(0,24 h) and C max (0,24 h) was increased by an average of 44% (95% CI 17, 78%) and 45% (95% CI 14, 85%), respectively. Saquinavir in combination with rifabutin was well tolerated. Gastrointestinal intolerance and asymptomatic increases in liver enzymes were the only adverse events of note. Conclusions Administration of rifabutin with saquinavir may decrease the efficacy of this HIV protease inhibitor.
The incidence of reduced bilirubin levels in 168 outpatients with epilepsy, compared with levels in 69 controls, has been investigated. Highly significant (p less than 0.001) reductions in average bilirubin levels were noted for carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), and multiple drug groups. A marginally significant (p less than 0.05) reduction in bilirubin levels occurred in patients treated with valproate (VPA) which, unlike the other drugs, has not been shown to induce hepatic enzymes.
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