Cyclosporine is a marketed immunosuppressive agent and a known substrate for CYP3A. Micafungin is an antifungal agent and a mild inhibitor of CYP3A-mediated metabolism in vitro. The objectives of this study were to evaluate the pharmacokinetics of cyclosporine and micafungin before and with concomitant administration. The pharmacokinetics of single-dose oral cyclosporine (5 mg/kg) were estimated on days 1, 9, and 15 (n = 27). Subjects received micafungin (100 mg/d over 1 hour) on days 7, 9, and 11 through 15. Micafungin pharmacokinetics were estimated on days 7, 9, and 15. Mean apparent oral cyclosporine clearances were estimated to be 645+/-236 mL/h/kg, 546+/-101 mL/h/kg (P = .01), and 540+/-104 mL/h/kg (P = .02) for days 1, 9, and 15, respectively. Micafungin appears to be a mild inhibitor of cyclosporine metabolism.

Following a caudal block with ropivacaine 2 mg x kg(-1) plasma concentrations of unbound ropivacaine were well below threshold levels for toxicity in adults. Apparent volume of distribution is unchanged, apparent unbound clearance increases and the terminal half-life decreases with age in 0-12-month-old neonates and infants. The postoperative pain management provided adequate analgesia and was well tolerated.

After the caudal epidural administration of levobupivacaine 2 mg kg(-1) in children less than 2 yr of age, C(max) was within the accepted safe range for racemic bupivacaine. T(max) varied and occurred later in some children, particularly those aged less than 3 months. Sampling in future pharmacokinetic studies in this age group should extend beyond 60 min.

Levobupivacaine is a promising new local anaesthetic agent for pain management in paediatric patients and appears to offer similar anaesthetic efficacy to racemic bupivacaine with a potentially improved tolerability profile.

No abstract

The acute hemodynamic effects of either ethacrynic acid or furosemide were studied in 27 patients who underwent diagnostic right and transseptal left heart catheterization. Twenth-three patients had postcapillary pulmonary hypertension secondary to isolated or predominant mitral stenosis. Of these, 21 patients were in New York Heart Association functional class III, and one each in class II and IV. In the remaining four patients pulmonary artery pressures were normal. Two patients had aortic stenosis and one each coronary artery disease and nonobstructive cardiomyopathy. All four patients were in class II. Cardiac index, pressures, and pulmonary blood volume (PBV) were measured in the control state and 20, 40, and 60 min after diuretic administration. Pulmonary extravascular fluid volume (PEV) was measured in the control state and at 60 min post drug infusion. A similar hemodynamic response was observed for each drug. Significant reductions in pulmonary artery and left atrial mean pressures, cardiac index, and plasma volume occurred over the one hour observation period and were accompanied by a significant duiresis. However, despite recutions in central pressures and blood flow, PBV, ev, and PEV/PBV remained unchanged, as did systemic arterial pressure. Since 23 of the subjects had postcapillary pulmonary hypertension it is postulated that the failure of PBV to decrease significantly despite significant decreases in pulmonary artery mean pressure is related to altered pressure volume characteristics in the pulmonary vascular bed in which the lung is operating on a steep portion of its pressure volume curve. The failure of the PEV to decrease supports the concept that the pulmonary extravascular space is relatively resistant to early decreases in pulmonary capillary pressure induced acutely. The failure of the pulmonary extravascular fluid volume to decrease despite a fall in plasma volume and pressures corresponds to the well recognized delay in resolution of radiologic evidence of pulmonary congestion.

No abstract

First heart sound (S1) energy spectra in isovolumic systole, hemodynamics, and angiographic left ventricular wall motion (LVWM) at rest and with atrial pacing were compared in 27 patients who underwent diagnostic cardiac catheterization and angiography because of chest pain. Eighteen patients were found to have coronary artery disease (CAD) and nine patients, normal coronary arteries. Eleven of the 18 CAD patients (61%) had a mean reduction in the spectral energy of S1 of 6.5 +/- 1.4 (SEM) dB below control (-52%), during interruption of ischemic stress of rapid atrial pacing, compared to only one of nine patients without CAD (P less than 0.05). Only five CAD patients (28%) had an abnormal rise (greater than or equal to 5 mm) in left ventricular end-diastolic pressure (LVEDP) either during or upon interruption of pacing, and six (33%) had ischemic ST-segment depression greater than or equal to mv in the ECG. Similarly two patients free of CAD (22%) had an abnormal increase in LVEDP, and none had ECG evidence of ischemia. Seventeen CAD patients (94%) had segmental LVWM abnormalities at rest or with interruption of pacing, while three patients with normal coronary arteries (33%) had abnormal angiographic LVWM (P less than 0.01). Thus, reduction is S1 spectral energy is a common accompaniment of myocardial ischemia. In the present study, it was more frequently observed than abnormalities in either the ECG or LVEDP, but was not was consistently seen as segmental left ventricular wall motion abnormalities.