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C Hoyo-Vadillo

Publications and source records attributed to C Hoyo-Vadillo.

At least 19 recordsLinked to original sources
PubMed1995

Pharmacodynamic interaction between midazolam and a low dose of ethanol in vivo.

The pharmacokinetic and pharmacodynamic interactions between midazolam and ethanol were studied in the rat in vivo. Ethanol was given as a constant rate intravenous infusion (1.85 mg/min). The pharmacokinetics and pharmacodynamics of midazolam were determined following an intravenous dose of 5 mg/kg in 15 minutes. Amplitudes in the 11.5-30 Hz (beta) frequency band of the EEG was used as a measure of the pharmacological effect. Ethanol infusion resulted in a constant plasma alcohol concentration of 0.44 +/- 0.04 g/l (Mean +/- SE) and had no effect on the baseline value of the EEG effect parameter. Also the pharmacokinetics of midazolam were unchanged. However, a significant parallel shift of the midazolam concentration-EEG effect relationship to lower concentrations was observed. These findings show that there is a pharmacodynamic interaction between midazolam and ethanol in vivo.

Animals↗
PubMed1995

Usefulness of the pain-induced functional impairment model to relate plasma levels of analgesics to their efficacy in rats.

In this work we show that the pain-induced functional impairment model (PIFIR) can be used with cannulated rats as a useful procedure for pharmacokinetic/pharmacodynamic modelling. This model evaluates analgesia by measuring motor impairment of the right limb after intra-articular administration of uric acid. Time of contact with a rotating cylinder is referred to the control limb. We studied the pharmacokinetic and pharmacodynamics of naproxen after six peroral doses to Wistar rats, and we examined the adjuvant action of caffeine with naproxen. Surgery and blood sampling did not produce any difference on functional impairment either in rats without uric acid or in the dysfunction produced by uric acid. The relation between naproxen plasma concentration and the analgesic effect was obtained with few rats. Caffeine alone did not produce any significant modification in functional impairment but the co-administration significantly increased the effect of naproxen. Plasma levels of naproxen did not change when caffeine was co-administered. The PIFIR model with blood sampling is a suitable method for pharmacokinetic/pharmacodynamic relationship studies and is specially useful to characterize drug-drug interactions.

Analgesics↗
PubMed1995

Relationship between naproxen plasma concentration and its anti-inflammatory effect in experimental hepatitis.

The relationship between the plasma concentration and the anti-inflammatory effect of naproxen (CAS 22204-53-1) after oral administration of a 6 mg.kg-1 dose was studied in rats with galactosamine-induced acute hepatitis and under control conditions. In control animals naproxen peak plasma levels of 35 +/- 0.4 micrograms.ml-1 were reached in 0.5 +/- 0 h. Concentration then decayed, half-life being 5.2 +/- 0.4 h. AUC was 131 +/- 5 micrograms.h.ml-1. In intoxicated rats peak plasma levels of 29 +/- 0.3 micrograms.ml-1 were reached in 0.7 +/- 0.1 h, half-life was increased to 11.1 +/- 1.3 h, and the AUC reached 259 +/- 21 micrograms.h.ml-1. In control rats the protective effect of naproxen against carrageenan-induced inflammation increased slowly, reaching a maximum of 38% in 4 h. The protective effect against plasma concentration curve exhibited a clear counterclockwise hysteresis, probably due to a slow naproxen transport from the circulation to its site of action. In animals with hepatitis, the protective effect remained quite constant at about 40% despite variations in plasma levels, probably because the maximal effect was reached. No clear hysteresis was observed in the effect-plasma concentration curve, suggesting that naproxen arrival to its site of action was faster. Results show that the relationship between naproxen plasma concentration and its anti-inflammatory effect is complex and therefore predictions on the pharmacological response in liver damage cannot be readily made by solely considering pharmacokinetic data.

Animals↗
PubMed1995

Differences in nifedipine concentration-effect relationship between capsule and slow release tablet administration.

The relationships between nifedipine plasma concentrations and its hypotensive and positive chronotropic effects were studied in healthy volunteers who received either a 10 mg capsule (CAP) or a 20 mg slow release tablet (SRT). Plasma concentrations rose more rapidly after CAP than after SRT, Cmax being 131 +/- 39 and 40 +/- 7 ng/ml and tmax being 0.5 +/- 0.07 and 1.8 +/- 0.4 h, respectively. Both formulations produced a reduction in diastolic blood pressure which exhibited a significant linear correlation (p < 0.01) with nifedipine plasma concentration. However, the slope obtained with SRT was significantly higher than that of CAP (0.24 +/- 0.05 vs 0.07 +/- 0.01, p < 0.01). That is, a similar hypotensive effect was produced at a lower concentration with SRT than with CAP. A positive chronotropic effect which exhibited a highly significant correlation with nifedipine plasma concentration (p < 0.0001) was observed with CAP. Conversely, with SRT heart rate increase was smaller and there was no significant correlation with nifedipine plasma concentration (p > 0.45). Since the measured decrease in blood pressure is the outcome of nifedipine-induced vasodilation and of homeostatic responses, results are interpreted as follows. Fast nifedipine input after CAP induced a brisk change in physiological conditions and hence triggered an important homeostatic response, visualized as heart rate increase, which partially offset the hypotensive effect. With SRT, there was a gradual change in blood pressure producing lesser activation of compensatory mechanisms and therefore the hypotensive effect of nifedipine was less antagonized than with CAP. Nifedipine SRT does not only exhibit pharmacokinetic advantages, but also a more favorable pharmacodynamic profile than CAP.

Adult↗
PubMed1993

Pharmacokinetics of oral nifedipine in different populations.

Nifedipine disposition varies among populations. Reports on oral nifedipine pharmacokinetics show that peak plasma levels and AUC values are higher in Mexican and Japanese than in European and North American subjects. Increased nifedipine bioavailability in the nonwhite populations is likely due to nutritional habits. Certain flavonoids that inhibit the first-pass metabolism of dihydropyridines are present in the diets of both Mexican and Japanese. Differences in phenotypes may play a role in interethnic variability.

Administration, Oral↗
PubMed1993

Pharmacokinetics and pharmacodynamics of naproxen in acute experimental hepatitis.

The pharmacokinetics of intravenous naproxen (CAS 22204-53-1) 6 mg kg-1, were studied in Wistar rats under control conditions and 1, 3 and 10 days after the induction of acute hepatitis by a single intraperitoneal injection of galactosamine 375 mg kg-1. In non-intoxicated rats t1/2 was 5.31 +/- 0.90 h, Vd was 0.21 +/- 0.01 l.kg-1, Cl was 17 +/- 5 ml.h-1.kg-1, AUC was 354.4 +/- 8.8 micrograms.h.ml-1 and 99.18 +/- 0.09% of naproxen was bound to plasma proteins. One day after intoxication the liver was considerably damaged; cytochrome P450, the main enzymatic system for naproxen metabolism, was decreased in 90%. Naproxen t1/2 was increased to 11.9 +/- 1.2 h but Vd did not change significantly, therefore clearance was reduced to 37%. Binding to plasma proteins was decreased to 83.21 +/- 0.27%. At day 3 liver function and naproxen pharmacokinetics exhibited a partial recovery, t1/2 was 6.59 +/- 0.92 h and clearance was 12.2 +/- 5 ml.h-1.kg-1 being not significantly different from controls; notwithstanding AUC was still significantly different from that of non-intoxicated rats. 10 days after galactosamine injection all pharmacokinetic parameters, as well as those of liver function, returned to basal levels. The results indicate that acute hepatitis produces an important reduction in naproxen elimination. Changes in naproxen disposition, which exhibit a time course similar to that of liver damage, are mainly determined by a decrease in intrinsic hepatic clearance and in the binding to plasma proteins.

Animals↗
PubMed1989

Pharmacokinetics of oral nifedipine: relevance of the distribution phase.

Pharmacokinetics of oral Nifedipine was studied in 12 Mexican young healthy volunteers, six men and six women, who received a 10 mg capsule. Plasma levels were determined by a nifedipine specific HPLC assay. Experimental data were fitted and pharmacokinetic parameters were calculated using an open two compartment model. No statistically significant difference was detected between men and women, thus both sexes were considered as a single population. Nifedipine plasma levels rose rapidly (ka = 8.46 +/- 1.96 h-1) reaching a maximum concentration of 145 +/- 23 ng/ml in 0.61 +/- 0.07 h. Plasma levels then decayed with a distribution phase (alpha = 1.98 +/- 0.40 h-1, t1/2 alpha = 0.46 +/- 0.06 h) and a terminal elimination phase (beta = 0.17 +/- 0.03 h-1, t1/2 beta = 4.98 +/- 0.55 h). AUC was 384 +/- 41 ng h/ml. Values of AUC and t1/2 beta were higher than those reported by other authors. Differences in the AUC could be due to ethnic origin, environmental factors or nutritional habits. Ten subjects presented plasma concentration-time curves in which the distribution phase was clearly distinguishable, having a ka/alpha relationship higher than 1.5. For the other two subjects, the distribution phase was not apparent and ka/alpha was lower than 1.5. The results show that an adequate characterization of the distribution phase is required if one pretends to use pharmacokinetic data for dosage regimen design.

Administration, Oral↗
PubMed1989

Pharmacokinetics of nifedipine slow release tablet in Mexican subjects: further evidence for an oxidation polymorphism.

Nifedipine kinetics after ingestion of 20 mg slow release tablets were studied in 12 young, healthy, Mexican subjects. Plasma levels were determined by a nifedipine-specific HPLC assay. Levels rose after drug administration reaching a maximum concentration of 48.7 +/- 7.3 ng/ml in 2.1 +/- 0.7 h (mean +/- SEM). Concentrations then decayed with a terminal half-life of 16.9 +/- 3.1 hours. AUC was 526 +/- 62 ng h/ml. Five individuals were fast and seven were slow nifedipine metabolizers, according to the AUC criterion proposed by Kleinbloesem and coworkers. Individual AUC/Dose values from this and from other two studies on oral nifedipine kinetics in Mexicans were cumulated and the frequency histogram and probit analyses were performed (N = 30). A bimodal distribution was clearly observed. Fast and slow metabolizers were distinguished as those subjects with AUC/Dose values either lower or higher than 22.5 ng h/ml mg. Unlike European populations, it appears that slow metabolization is more frequent in Mexicans. Data strongly support the hypothesis of the existence of a polymorphism concerning nifedipine disposition kinetics due to genetic basis.

Adult↗