Safety, tolerability and pharmacokinetics of intravaginal pentamycin.
OBJECTIVE
Intravaginal pentamycin is a polyene macrolide with a broad spectrum of antimicrobial activity and is effective in various forms of infectious vaginitis. We evaluated the safety, tolerability and pharmacokinetics of escalating doses of this product.


METHODS
Nineteen healthy volunteers were randomized to receive double blind one of five doses of intravaginal pentamycin (3, 10, 30, 60 or 100 mg) or the corresponding dose of pentamycin vehicle daily for 6 days. Patients with symptomatic vaginitis received a single dose of 60 (n = 6) or 100 mg (n = 6) of intravaginal pentamycin. Safety and tolerability parameters were monitored throughout the study. Plasma concentrations of pentamycin were measured daily in the healthy volunteers and on the day of drug application in the patients.


RESULTS
The most frequently reported adverse events were mild or moderate vaginal discharge and mild symptoms of vaginal irritation (mainly pruritus or burning sensation), which also occurred in women who applied the vehicle. No patient with symptomatic vaginitis reported treatment-related adverse events. The plasma levels of pentamycin were below the quantification limit in all samples.


CONCLUSIONS
Intravaginal pentamycin does not cause adverse reactions compared with vehicle and is not absorbed through the intact or the inflamed vagina.
Frey Tirri
B
B
Department of Obstetrics and Gynecology, University Hospital Basel, Basel, Switzerland. bfrey @ uhbs.ch
Bitzer
J
J
Geudelin
B
B
Drewe
J
J
D015746:Abdominal Pain / Q000139:chemically induced; D000282:Administration, Intravaginal; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D018942:Macrolides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D008875:Middle Aged; D011090:Polyenes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D014621:Vagina / Q000187:drug effects* / Q000378:metabolism*; D019522:Vaginal Discharge / Q000139:chemically induced; D016585:Vaginosis, Bacterial / Q000097:blood / Q000188:drug therapy; D055815:Young Adult
D018942:Macrolides; D011090:Polyenes; C011827:fungichromin