Low-dose prazosin in patients with muscle cramps during hemodialysis.

Sympathetic nervous system response to volume stress is more marked in patients with frequent hemodialysis-associated skeletal muscle cramps than in most patients who cramp infrequently. Accordingly, we conducted a double-blind, randomized, and balanced trial in which five patients with frequent hemodialysis-associated cramps were given either placebo or a prazosin dose (ranging from 0.25 to 1.0 mg) at the start of 16 dialysis sessions. These low doses of prazosin appeared to reduce cramp frequency in four of the five patients, and patient-stratified multiple logistic regression analysis indicated an aggregate 58% reduction in cramp frequency (p = 0.030). On the other hand, prazosin therapy was associated with an increased incidence of hypotension that required therapeutic intervention both during (p = 0.033) and after (p = 0.010) hemodialysis. Our findings support the hypothesis that sympathetic activation plays a pathogenetic role in hemodialysis-associated skeletal muscle cramps and suggest that pharmacologic attenuation of this response may be of therapeutic benefit.

Simultaneous analysis of inulin and 15N2-urea kinetics in humans.

To elucidate the physiologic basis of multicompartmental systems used to model drug distribution, we studied inulin and 15N2-urea kinetics after simultaneous intravenous injection in five normal subjects. Distribution of both compounds was characterized by three-compartment models in which the central compartment corresponded to intravascular space. The mean distribution volumes of 0.164 +/- 0.009 L/kg (+/- SD) for inulin and of 0.670 +/- 0.143 L/kg for urea were similar to expected values for extracellular space and total body water, respectively. Distribution from intravascular space was kinetically heterogeneous, presumably reflecting differences in vascular beds supplied by either fenestrated and discontinuous capillaries or capillaries with a continuous basement membrane. Intercompartmental clearances of inulin and urea and the ratio of their free water diffusion coefficients were used to estimate blood flows and permeability coefficient-surface area products for the peripheral compartments. The sum of compartmental blood flows averaged 5.39 +/- 0.49 L/min and was similar to dual-beam Doppler measurements of cardiac output (5.47 +/- 0.40 L/min).

Pharmacokinetics of prednisolone transfer to breast milk.

Prednisolone transfer to breast milk was studied in three nursing women who required oral steroid therapy for asthma. Each patient received a 50 mg intravenous dose of prednisolone phosphate, and blood and breast milk were sampled for 6 hours. Concentrations of prednisolone in milk declined more rapidly than in serum but were similar to expected unbound serum concentrations, suggesting that exchange between unbound prednisolone in serum and breast milk is relatively rapid and bidirectional. Because an average of 0.025% (range, 0.010% to 0.049%) of the prednisolone dose was recovered in milk, prednisolone transfer to breast milk does not appear to pose a clinically significant risk to nursing infants.