British journal of clinical pharmacology
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Br J Clin Pharmacol · Aug 1994
Clinical TrialReproducibility of non-invasive measurement and of short-term variability of blood pressure and heart rate in healthy volunteers.
1. Spectral analyses of blood pressure and heart rate oscillations are increasingly used to assess the influences of diseases and drugs on the autonomic nervous system. Such influences can only be interpreted in view of the spontaneous variability of these oscillations. ⋯ The standard deviation of differences between systolic blood pressure or heart rate oscillations on different occasions was in the 150-200 and 50-100 mm Hg Hz-1/2 or beats min-1 Hz-1/2 range for low frequency and high frequency oscillations respectively. Similar results were found when inter-observer reproducibility was considered. 4. From these results, we derived a sample-size table giving the number of subjects to be included in studies of cross-over or parallel design in order to detect a non-random difference in spectral analysis parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
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Br J Clin Pharmacol · Aug 1994
Clinical TrialPharmacokinetics of the enantiomers of bupivacaine following intravenous administration of the racemate.
1. The pharmacokinetics of R(+)-bupivacaine and S(-)-bupivacaine were investigated following a 10 min intravenous infusion of the racemate (dose 30 mg) in 10 healthy males. 2. The fractions unbound of R(+)- and S(-)-bupivacaine in pre-dose plasma were determined for each subject after in vitro addition of rac-bupivacaine (concentration of each enantiomer: approximately 300 ng ml-1). 3. ⋯ The plasma clearance of unbound R(+)-bupivacaine (7.26 +/- 3.60 1 min-1) was smaller (P < 0.01) than that of S(-)-bupivacaine (8.71 +/- 4.27 l min-1). Volumes of distribution based on unbound R(+)-bupivacaine concentrations (Vuss: 1576 +/- 934 l; Vu: 2233 +/- 1442 l) did not differ from those of S(-)-bupivacaine (Vuss: 1498 +/- 892 l; Vu: 1978 +/- 1302 l). 6. The enantioselective systemic disposition of bupivacaine can to a large extent be attributed to differences in the degree of plasma binding of the enantiomers.