Oral ganciclovir has recently been approved for use in long-term maintenance therapy in the treatment of cytomegalovirus (CMV) retinitis in immunocompromised patients. Although oral ganciclovir at a dose of 3,000 mg/d is moderately less effective than intravenous (i.v.) ganciclovir maintenance therapy (5 mg/kg as a 1-hour i.v. infusion every 24 hours), convenience and practicality make oral maintenance therapy desirable. Two dosing regimens--1,000 mg three times daily (TID) and 500 mg every 3 hours (six times daily)--have been shown to be efficacious. Eighteen human immunodeficiency virus- and CMV-seropositive patients participated in a three-way, open-label, crossover study to evaluate the steady-state pharmacokinetics and absolute bioavailability of the two oral regimens compared with the i.v. regimen. Sixteen patients completed the study and received ganciclovir as a single 5-mg/kg i.v. infusion over 1 hour, 500 mg orally every 3 hours while awake (six times daily) for 3 days, and 1,000 mg TID orally for 3 days. Blood samples were obtained over a 24-hour period after the single i.v. dose and on day 3 of the oral dosing regimens. Mean peak serum concentrations were 8.27, 1.02, and 1.18 micrograms/mL for the i.v. and oral regimens, respectively. Twenty-four-hour area under the curve (AUC) for the oral regimens--500 mg every 3 hours and 1,000 mg TID--were 15.9 and 15.4 micrograms.h/mL, respectively, as compared with a total AUC of 22.1 micrograms.h/mL for the single i.v. dose. The absolute bioavailabilities for the two oral regimens were 8.84% and 8.53%, respectively. The extent of ganciclovir absorption, peak concentrations, and average concentration at steady state were not statistically different between the two oral regimens. The peak-to-trough concentration ratio (Cmax:Cmin) was greater for the 1,000-mg TID regimen than for the regimen of 500 mg every 3 hours (5.35 vs 3.81 [P < 0.01]). Both oral regimens resulted in concentrations in the range of the concentration that inhibits 50% of most human CMV isolates. Because both oral regimens provide equivalent absorption, the 1,000-mg TID regimen may be preferred for the convenience and potentially greater compliance associated with fewer daily doses.

Administration, Oral↗

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The effect of intra-aortic balloon counterpulsation on coronary blood flow velocity distal to coronary artery stenoses.

Despite the accepted clinical benefit of intra-aortic balloon counterpulsation (IABC), the physiologic explanation for its benefit remains controversial. Indirect methods of measuring coronary blood flow during IABC in obstructive coronary disease have yielded conflicting results. The direct measurement of coronary blood flow velocity distal to sites of stenoses by methods that do not potentially impede flow has not been previously reported. The aim of our study was to determine the effect of IABC on coronary blood flow velocity distal to a coronary stenosis by employing a method that would not impede flow through the stenosis. In an open-chest canine model, phasic and mean left anterior descending coronary artery flow velocities distal to varying degrees of stenosis were continuously measured by an epicardial Doppler probe with and without counterpulsation. All hemodynamic parameters were recorded in the absence of stenosis (n = 5) and the presence of subcritical (n = 5) and critical stenoses (n = 5). Heart rate was not affected by counterpulsation. Systolic blood pressure and rate-pressure product declined at all times with IABC. Compared to baseline, peak aortic diastolic pressure was augmented by an average of 24 mm Hg during IABC (p < 0.05). However, mean coronary artery flow velocities remained unchanged (101, 103 and 98% of baseline for no stenosis, subcritical stenosis and critical stenosis, respectively; p > 0.05 compared to baseline). Peak diastolic flow velocities were 106, 102 and 96% of baseline for no stenosis, subcritical and critical stenoses, respectively (p > 0.05). Despite the augmentation of peak diastolic pressure, distal coronary blood flow velocity was not increased by IABC in this canine model, irrespective of the severity of proximal coronary stenosis. These data suggest that augmentation of coronary artery flow distal to sites of stenoses is not primarily responsible for the clinical benefit observed when IABC is used in the setting of obstructive coronary artery disease. The reduction in afterload and myocardial oxygen demand observed in this model agrees with previous studies and likely accounts, at least in part, for the positive clinical results with IABC.

Animals↗

PubMedDate not supplied

Parotid lipomatosis in a 2-month-old child.

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Humans↗