A randomized, double-blind, pharmacokinetic study of oral maribavir with tacrolimus in stable renal transplant recipients.

Maribavir is being developed as a novel agent for the prevention or treatment of cytomegalovirus infections after stem cell and organ transplantation. This was a randomized, double-blind, placebo-controlled study designed to evaluate the potential pharmacokinetic interaction of concomitant administration of maribavir and tacrolimus. Twenty-five adult renal transplant recipients with stable renal function and stable dosing regimens of tacrolimus were randomized (20 maribavir 400 mg p.o. q12 h: 5 placebo). Tacrolimus whole blood concentration profiles were determined before and after 7 days of co-administration with maribavir. When co-administered with maribavir, tacrolimus mean C(max) increased 38%, tacrolimus trough concentrations (12 h post-dose) increased 57% and tacrolimus AUC((0-tau)) increased 51%. Apparent oral clearance of tacrolimus decreased 34% and T(max) was delayed by 0.5 h. There were no serious adverse events and no subject prematurely discontinued treatment. Because of the limited 7-day dosing course, the adverse event profile could not be adequately assessed. However, as seen with other maribavir studies, dysgeusia was common (90% of maribavir subjects and 20% of placebo subjects). In conclusion, co-administration of maribavir 400 mg twice daily increases exposure to tacrolimus. Routine therapeutic drug monitoring of tacrolimus blood concentrations should be included both at initiation and completion of maribavir treatment.

Fluoroquinolones.

The fluoroquinolone class of antimicrobial agents has expanded dramatically in the last 5 years and will continue to grow over the next decade. This article discusses the newer fluoroquinolones in detail, including pharmacokinetics, pharmacodynamics, safety, and drug interactions, and the spectrum of in vitro activity. Newer agents are compared and contrasted with the older ones, particularly ciprofloxacin and ofloxacin, and problems with liver toxicity and trovafloxacin are described. Finally, appropriate use of the fluoroquinolones is discussed, including their role in the treatment of urinary tract infections, sexually transmitted diseases, gastrointestinal infections, osteomyelitis, and respiratory tract infections.

Difficult-to-treat trichomoniasis: results with paromomycin cream.

Vaginal trichomoniasis poses a difficult therapeutic challenge when metronidazole is ineffective or contraindicated. We conducted a retrospective study of 6.25% paromomycin cream in the treatment of nine women referred with cases of vaginal trichomoniasis where metronidazole resistance or allergy was present. Results obtained immediately and 1 month after treatment were reviewed. The median age of the patients was 46 years; four women were nulliparous. The median symptom duration was 1 year. Five women were allergic to metronidazole. In four cases, resistance to high doses of metronidazole was demonstrated. Smears or cultures were positive immediately after treatment for three patients; a fourth relapsed 2 weeks later. Of these patients for whom treatment failed, one was cured with a 3-week course of paromomycin cream, and another was successfully treated with paromomycin cream and oral tinidazole. Three patients developed vaginal ulcerations that resolved spontaneously. Adverse effects may be a result of local formulation. Paromomycin cream was useful for treatment of cases of trichomonas infection where metronidazole resistance or allergy was encountered.

Cromolyn cream for recalcitrant idiopathic vulvar vestibulitis: results of a placebo controlled study.

OBJECTIVE: Patients with chronic idiopathic vulvar vestibulitis have increased mast cells when biopsied, and cromolyn has been suggested as a treatment. The purpose of this study was to assess the efficacy of 4% cromolyn cream in women with vulvar vestibulitis. METHODS: A prospective, double blind, randomised, placebo controlled study was initiated at two centres. Patients with vulvar vestibulitis were assigned to apply cromolyn or placebo cream to the vestibule. Symptoms (burning, irritation) and signs (erythema, extent of erythema, tenderness) were recorded on a 0-3 scale. In the sexually active patient subgroup, dyspareunia was also evaluated. RESULTS: 13 of the 26 evaluable patients received cromolyn. Patients in the cromolyn arm were more likely to have failed therapy with amitriptyline (p = 0.05), but the two groups were otherwise similar upon study entry. Overall, scores decreased from a median of 9 to 5 (p = 0.001) during the study, but the level of improvement was similar between both groups. Improvement was unrelated to duration of symptoms, fluconazole use, or sexual activity. Five patients (38%) taking cromolyn and six (46%) taking placebo felt they had a 50% or greater reduction in symptoms. In the 21 sexually active patients, the total score decreased from a mean of 12 to 8 (p = 0.005), but there was no statistically significant difference between study arms. CONCLUSIONS: Cromolyn cream did not confer a significant benefit in patients with vulvar vestibulitis. The large placebo response suggests the need for large well controlled studies of other treatment modalities.