Comparative oral bioavailability of azimilide dihydrochloride in the fed and fasted states.

AIMS: This study investigated the relative oral bioavailability of azimilide dihydrochloride following administration in the fed (high-fat meal) and fasted states. METHODS: This was a single-dose, randomized, two-way crossover study in 30 healthy, Caucasian, male subjects. Following oral administration, blood samples were collected over 27 days and analysed for azimilide using h.p.l.c. with u.v. detection. Pharmacokinetic parameters were determined using 'noncompartmental' analysis and compared using an ANOVA and 90% or 95% confidence intervals. RESULTS: The extent of absorption was equivalent in the fed and fasted states (ratio = 96.2%; 90% CI=90.5% -102.4%). However, Cmax was decreased 19% following a high-fat meal (ratio=81.4%; 90% CI= 76.2% -87.0%). No difference in tmax or t(1/2),z was observed. CONCLUSIONS: Azimilide dihydrochloride may be orally administered to patients without regard to the prandial state.

Azimilide pharmacokinetics following intravenous and oral administration of a solution and capsule formulation.

Azimilide dihydrochloride (NE-10064) is a novel class III anti-arrhythmic agent that blocks both the slowly and rapidly acting components of the delayed rectifier potassium current of human atrial and ventricular myocytes. In clinical studies, azimilide reduced the frequency of symptomatic episodes of atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia. This study was conducted to characterize azimilide pharmacokinetics following single-dose administration of a 1 mg/kg intravenous infusion (18 min), 2 mg/kg oral solution, and a 150 mg orally administered capsule. This was a three-period, randomized, crossover study in 27 healthy, drug-free (including caffeine and alcohol), non-smoking male volunteers (mean [SD]; age, 25.9 [1.0] years; weight 74.3 [0.7] kg; 23 Caucasians and 4 Hispanics). Blood and urine samples were collected for 27 days and analyzed for azimilide using HPLC with UV detection. Subjects were monitored for adverse events and abnormalities in clinical laboratory tests, vital signs, and electrocardiography (including Holter monitoring). Mean (%CV) azimilide parameters were total clearance = 0.143 L/h/kg (38%), renal clearance = 0.014 L/h/kg (35%), steady-state volume of distribution = 13.2 L/kg (23%), and terminal exponential half-life = 78.8 h (44%). Similar parameter estimates were obtained following oral administration. Both the oral solution and capsule formulations were completely absorbed. In addition, the rate (Cmax) and extent of absorption (AUC) following oral administration of the capsule dosage form were bioequivalent to the oral solution with means for times of maximum blood concentration of 7.08 and 7.18 hours for the oral solution and capsule, respectively. Azimilide dihydrochloride was generally well tolerated in all subjects.

Maintenance of safe sex behavior by HIV-serodiscordant heterosexual couples.

We present findings from a prospective study of heterosexual HIV transmission in stable New Jersey couples who are serodiscordant for HIV and in which the uninfected partner is at risk solely from heterosexual contact. One hundred thirty-one couples were interviewed at enrollment and 6-month follow-up. This report describes couples' sexual behavior before and after knowledge of infective risk and examines associations of behavior with clinical and demographic characteristics. We observed that HIV serodiscordant couples' habitual sexual practices, drug and alcohol use, and measure of psychological distress may predict difficulty in adopting and maintaining safe sex. An understanding of common risk sexual behavior patterns and characteristic correlates of risk taking may prove useful for counseling individuals at risk and their infected partners and may contribute to the development of effective public health messages targeted to eliminate unsafe sexual contact.

PIP: Findings are presented from a prospective study of heterosexual HIV transmission in stable New Jersey couples serodiscordant for HIV infection and in which the uninfected partner is at risk solely from heterosexual contact. Between August 1990 and February 1992, 131 couples were interviewed at enrollment and 6-month follow-up, reporting their frequencies of vaginal, oral, and anal sex, with and without condoms, during the year before the negative partner learned of the positive partner's HIV infection, the month before baseline interview, and the interval between baseline and follow-up. A marked and significant decline was observed in couples' reported sexual activity and an increase in condom use after they first learned of their HIV serodiscordance. However, at the 6-month follow-up, the proportion who abstained from having sex declined from 33% to 21%, the proportion who practiced unsafe sex increased from 15% to 26%, and the proportion of couples who used condoms reliably was 53% at follow-up compared to 51% in the month before enrollment. Demographic characteristics, stage of disease in the HIV-infected partner, use of alcohol or drugs, and psychological state were correlates of unsafe sexual behavior after learning of HIV serodiscordance. The most important socioeconomic correlate of safe sex at baseline was employment of the female partner. People in stable partnerships may have greater difficulty changing well-established patterns of sexual behavior after one partner is found to be infected with HIV.