Journal of pharmaceutical sciences
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Randomized Controlled Trial
No clinically relevant pharmacokinetic and safety interactions of ambrisentan in combination with tadalafil in healthy volunteers.
Ambrisentan is a nonsulfonamide, ET(A)-selective endothelin receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH), and tadalafil is a phosphodiesterase type 5 (PDE-5) inhibitor under investigation for treatment of PAH. Due to the potential combination use, the pharmacokinetic (PK) interactions between these two drugs were assessed in a crossover study in 26 healthy adults. Single-dose PK of ambrisentan (10 mg) and its metabolite, 4-hydroxymethyl ambrisentan, were determined in the absence and presence of multiple doses of tadalafil (40 mg QD). ⋯ The safety profile of the drugs combined was similar to that of either drug alone. No dose adjustments should be necessary when these drugs are coadministered. These results are in contrast to previous reports that the sulfonamide-based ERA bosentan can cause marked decreases in the exposure of tadalafil.
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Randomized Controlled Trial Comparative Study Clinical Trial
Development and pharmacokinetic characterization of pulmonal and intravenous delta-9-tetrahydrocannabinol (THC) in humans.
The aim of the present study was to develop a physiologically compatible inhalation solution of delta-9-tetrahydrocannabinol (THC), and to compare the pharmacokinetic and analgesic properties of pulmonal THC versus pulmonal placebo and intravenous (iv) THC, respectively. Eight healthy volunteers were included in this randomized, double-blind, crossover study. The aqueous THC formulations were prepared by using a solubilization technique. iv THC (0.053 mg/kg body weight), pulmonal THC (0.053 mg/kg), or a placebo inhalation solution was administered as single dose. ⋯ The side effects observed after pulmonal THC were coughing and slight irritation of the upper respiratory tract, very mild psychotropic symptoms, and headache. The side effects after iv THC were much more prominent. Neither pulmonal nor iv THC significantly reduced experimentally induced pain.
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Randomized Controlled Trial Clinical Trial
Effect of dexmedetomidine on propofol requirements in healthy subjects.
Dexmedetomidine-propofol pharmacodynamic interaction was evaluated in nine healthy subjects in a crossover design. Dexmedetomidine/placebo was infused using a computer-controlled infusion pump (CCIP) to maintain a pseudo-steady-state plasma concentration of 0.66 +/- 0.080 or 0 ng/mL, respectively. Forty-five minutes after the dexmedetomidine/placebo infusion was started, propofol was infused using a second CCIP to achieve a stepwise logarithmically ascending propofol concentration (1.00 to 13.8 microg/mL) profile. ⋯ The apparent EC50 values of propofol (EC50APP; concentration of propofol at which the probability of achieving a pharmacodynamic endpoint is 50% in the presence of dexmedetomidine concentrations observed in the current study; dexmedetomidine treatment) were 0.273, 0.544-0.643, and 3.89 microg/mL for the ability to hold a syringe, sedation scores, and motor response, respectively. Dexmedetomidine reduced propofol concentrations required for sedation and suppression of motor response. Therefore, the propofol dose required for sedation and induction of anesthesia may have to be reduced in the presence of dexmedetomidine.