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Biomedical subjects

M G Bogaert

Publications and source records attributed to M G Bogaert.

At least 55 records · Page 3Linked to original sources
PubMed1990

Influence of exercise on nitroglycerin plasma concentrations after transdermal application.

Nitroglycerin plasma concentrations following transdermal application were measured in nine healthy subjects during supine rest position or during supine rest interrupted by sitting or exercising for 20 min. Sitting led to almost doubling of the average plasma concentrations (0.31 ng ml-1 before sitting, 0.55 ng ml-1 at the end of the sitting period), but exercise was accompanied by a much more marked increase in average plasma concentrations, which reached its maximum 5 min after ending exercise (0.22 ng ml-1 before exercise, 1.26 ng ml-1 5 min after the exercise period). Changes of bioavailability as well as of systemic clearance might be involved in the exercise-induced increase in plasma nitroglycerin concentrations.

Administration, Cutaneous↗
PubMed1990

Influence of lignocaine on plasma protein binding and pharmacokinetics of verapamil in dogs.

The effect of lignocaine (lidocaine) on the plasma protein binding of verapamil has been studied in-vitro and in-vivo in dogs. The binding of verapamil was ca 85%. In-vitro addition of lignocaine at therapeutic concentrations displaced verapamil from its plasma binding sites. Lignocaine in this regard was equipotent with tris(2-butoxyethyl)phosphate, suggesting an interaction at the level of alpha 1-acid glycoprotein binding sites. On in-vivo administration of 4 mg kg-1 in a bolus to dogs in which steady state concentrations of verapamil were present, the free fraction of verapamil increased transiently. During the lignocaine maintenance infusion, it then decreased to a level higher than that before administration of the local anaesthetic. The free verapamil concentrations increased suddenly upon the administration of the lignocaine loading dose, and then returned to values slightly higher than those before lignocaine. After a bolus injection of verapamil during a lignocaine infusion, the verapamil total plasma concentrations were lower than during a saline infusion, but the free concentrations were not different. The volume of distribution of verapamil was increased, whereas the blood clearance had not changed; the lignocaine infusion did not change the hepatic blood flow, as measured by indocyanine green clearance. These results show that lignocaine displaces verapamil in-vitro and in-vivo from its plasma protein binding sites, but the ensuing pharmacokinetic changes do not lead to significant changes in free verapamil concentrations.

Animals↗
PubMed1990

Penetration of ampicillin and sulbactam in the lower airways during respiratory infections.

We studied the penetration of ampicillin-sulbactam in the alveolar lining fluid (ALF) of eight patients after intravenous administration of 2,000 mg of ampicillin and 1,000 mg of sulbactam three times daily over 30 min. Bronchoalveolar lavage was performed on day 3, 30 min after the end of the morning drug administration. The mean penetration ratios (i.e., the ratios of the concentrations in ALF versus those in serum) were 53% (standard error, 12%) and 61% (standard error 31%) for ampicillin and sulbactam, respectively. The concentration ratio of ampicillin versus sulbactam in serum was not significantly different from that in ALF. From a pharmacokinetic point of view, ampicillin-sulbactam is a good choice for treatment of infectious exacerbation of chronic obstructive pulmonary disease and community-acquired bacterial pneumonia, since the concentrations of both drugs in ALF exceed the MICs for the respiratory pathogens responsible.

Aged↗
PubMed1990

Effect of aging on the pharmcokinetics of atenolol, metoprolol and propranolol in the rat.

The pharmacokinetics of three beta adrenoceptor blocking drugs atenolol, metoprolol, propranolol and of the model drug antipyrine were studied in 3-, 12- and 24-month-old rats. Alpha-1-acid glycoprotein in plasma was slightly increased and the free fraction of propranolol was slightly decreased in the 24-month-old rats. For the four drugs studied, the volume of distribution and the clearance were decreased in the older rats. For propranolol, metoprolol and antipyrine these decreases were already observed in 12-month-old rats, for atenolol only in the 24-month-old rats. There was no change in half-life as a function of age for the three beta blockers; for antipyrine a significant increase in half-life was seen. The decreased volume of distribution suggests a lower tissue binding or a decrease in total body fluid. The change in clearance in function of age can probably be explained for metoprolol and propranolol by a decrease in hepatic blood flow as no change in metabolism or protein binding occurs, for atenolol by a decrease in renal function and for antipyrine by a decrease in metabolism. After p.o. administration of the beta blockers, no significant increase in area under the plasma drug concentration-time curve was observed for propranolol and metoprolol as a function of age, but for atenolol, a significant increase in area under the plasma drug concentration-time curve was seen in the 24-month-old rats, due to a decrease in renal function, as bioavailability of atenolol did not change in function of age.

Aging↗
PubMed1989

Plasma concentrations and haemodynamic effects of nimodipine in patients resuscitated after cardiac arrest.

As the pharmacokinetics of a drug may be altered in haemodynamically compromised patients, the plasma concentrations and haemodynamic effects of the calcium entry blocker nimodipine have been examined in patients resuscitated after out-of-hospital cardiac arrest. In 7 patients nimodipine was infused at increasing rates up to 30 micrograms.kg-1.h-1. The plasma concentrations increased with increasing dose; at the highest dose a mean steady-state plasma concentration of 22.1 ng.ml-1 was obtained, and the mean plasma clearance was 1.41.kg-1.h-1. There were no marked changes in mean arterial blood pressure or heart rate. In 9 other patients nimodipine was given as a bolus infusion of 10 micrograms.kg-1 over 3 min, followed by a continuous infusion of 30 micrograms.kg-1.h-1. A mean steady-state plasma concentration of 17.6 ng.ml-1 was obtained and the mean plasma clearance was 1.91.kg-1.h-1. Heart rate did not change significantly, but the mean arterial blood pressure fell. The data indicate that in patients resuscitated after cardiac arrest, the pharmacokinetics of nimodipine are not markedly different from patients with other conditions, e.g. subarachnoid haemorrhage. However, if a loading dose is given to obtain a steady-state concentration sooner, there will be a fall in arterial blood pressure.

Adult↗
PubMed1989

Neurological damage in a cardiopulmonary arrest model in the rat.

In view of the interest in cerebral protection in the framework of cardiopulmonary arrest (CPA), we assessed the neurological damage in a CPA model in the rat. CPA was induced in anesthetized Wistar rats by discontinuation of the jet ventilation and intracardiac injection of KCl. The animals were resuscitated after a CPA of either 7 min, 10.5 min, or 14 min. Six rats were used as nonischemic controls. All nonischemic rats survived, whereas in the resuscitated rats the 7-day survival rate decreased with increasing CPA duration. In the resuscitated rats, the neurological score was worse than in the control rats, and the score after 10.5-min CPA was worse than after 7-min CPA. Seizures were observed in 68% of resuscitated rats. Histopathological evaluation revealed moderate but selective neuronal necrosis in the hippocampus of all ischemic rats, and no cortical necrosis. However, neither the occurrence of seizures nor the extent of neuronal necrosis was related to the CPA duration. We conclude that in this model survival rate, neurological score, occurrence of seizures, and histopathological assessment can be used to evaluate neurological damage, although the contribution of other organ failure to these effects cannot be excluded.

Animals↗
PubMed1989

Effect of turpentine-induced inflammation on the disposition kinetics of propranolol, metoprolol, and antipyrine in the rat.

Plasma concentrations after oral administration of the high extraction drug propranolol are increased in patients and animals with inflammation. This could be due to increased serum propranolol binding, but also to decreased first-pass metabolism. We studied the pharmacokinetics of 3 drugs in control rats and in rats with turpentine-induced inflammation: propranolol, which is bound extensively to alpha 1-acid glycoprotein (alpha 1-AGP); metoprolol, another high extraction drug, but which is negligibly bound to alpha 1-AGP; and antipyrine, a low extraction drug, not bound to serum proteins. After IV administration of propranolol in rats with inflammation, systemic clearance, volume of distribution, and free fraction decreased, and the area under the curve (AUC) increased, whereas the half-life did not change. As the systemic clearance of a high extraction drug such as propranolol depends on hepatic blood flow only, a fall in hepatic blood flow or transition to a low extraction situation should be postulated. After oral administration of propranolol, the AUC was increased 20-fold in rats with inflammation; as the decrease in free fraction was only 4-fold, it can be concluded that a considerable decrease in hepatic intrinsic clearance was present. For metoprolol, in contrast to propranolol, after IV administration, no changes in pharmacokinetic parameters as a result of inflammation were observed. After oral administration, the AUC was increased about 4 times in rats with inflammation; as metoprolol is only negligibly bound to serum proteins, the increase in AUC can be attributed to a decrease in hepatic intrinsic clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Cardiopulmonary bypass and the pharmacokinetics of drugs. An update.

Cardiopulmonary bypass is accompanied by profound changes in the organism that may alter the pharmacokinetics of drugs. Drug distribution can be altered, for example, by changes in blood flow and by haemodilution, with a decrease in protein binding; a decrease in the elimination of some drugs can be caused by impairment of renal or hepatic clearance, due, for example, to lowered perfusion and hypothermia. The subject was reviewed in the Journal in 1982, and the emphasis of the present review is on new data related to specific drugs. The following substances are dealt with: benzodiazepines, cephalosporins, digitalis glycosides, general anaesthetics, glyceryl trinitrate (nitroglycerin), lignocaine (lidocaine), muscle relaxants, nitroprusside, opiates, papaverine and propranolol. For many of these substances an abrupt decrease has been observed in serum concentration upon initiation of bypass, which is explained by haemodilution and an increase in distribution due to decreased protein binding. For nitrates and some opiates, adsorption to the bypass apparatus was shown to be important. The gradual increase in serum concentrations seen during cardiopulmonary bypass with some drugs after the initial fall is usually explained by redistribution of the drug and/or decrease in its elimination. The same phenomena are thought to explain why in the post-bypass period a concentration increase occurs, or at least a slower decrease than expected. However, drug elimination has been directly measured in only a few studies. The short duration of the bypass procedure and the continuous changes during the process hamper a rigorous pharmacokinetic evaluation. Studies allowing more precise understanding of the mechanisms underlying the observed concentration changes are needed, but are difficult to design. Similarly, more data are awaited on the pharmacodynamic and clinical consequences of the concentration changes.

Anesthetics↗
PubMed1989

Comparative pharmacokinetics of recombinant erythropoietin administered by the intravenous, subcutaneous, and intraperitoneal routes in continuous ambulatory peritoneal dialysis (CAPD) patients.

The single dose pharmacokinetics of recombinant human erythropoietin (r-HuEPO) were compared in six continuous ambulatory peritoneal dialysis (CAPD) patients after intravenous (i.v.), subcutaneous (s.c.), and intraperitoneal (i.p.) administration of 300 U/kg. Intravenous administration gave results close to those obtained in hemodialysis patients, with a half-life of 11.2 h and a volume of distribution of 5.0% of body weight. After subcutaneous administration, the serum concentration rose slowly to plateau between 24 and 36 h, the area under the serum concentration vs. time curve from 6 to 72 h being 18.2% of that after intravenous administration. After intraperitoneal administration, the serum concentration was even lower, the area under the curve from 0 to 24 h was between 2.5 and 3.6% of that after intravenous administration, and 80% of the administered dose was recovered in the first peritoneal effluent after a 4-h dwell time.

Aged↗
PubMed1988

Influence of continuous ambulatory peritoneal dialysis on serum alpha 1-acid glycoprotein concentration and drug binding.

The influence of continuous ambulatory peritoneal dialysis (CAPD) on the concentrations of alpha 1-acid glycoprotein in serum and dialysate and on the serum binding of oxprenolol, propranolol and phenytoin has been studied. Before starting CAPD treatment, the serum binding of oxprenolol and propranolol was higher and that of phenytoin lower than in healthy volunteers, and the serum alpha 1-AGP concentration was higher. During the first days to weeks after starting CAPD, the serum alpha 1-AGP concentration rose with a concomitant increase in the binding of oxprenolol and propranolol. Subsequently, the alpha 1-AGP level and the binding of oxprenolol and propranolol decreased to the values found before starting CAPD. The binding of phenytoin showed little change. The concentration of alpha 1-AGP in dialysate was 2 to 5% of that in serum.

Adult↗
PubMed1988

Influence of exercise on plasma concentrations of isosorbide dinitrate.

As the fall in hepatic blood flow caused by exercise is expected to decrease the elimination of high extraction drugs, the influence of exercise on the fate of the anti-anginal drug isosorbide dinitrate has been assessed. Isosorbide dinitrate 10 mg was given orally, after an overnight fast, on 2 different days to 7 healthy volunteers and the plasma concentrations of the parent compound and its mononitrate metabolites were measured. Heavy bicycle exercise from the 45th to the 105th min after intake of the drug on one of the experimental days did not change the plasma isosorbide dinitrate concentrations as compared to those on the rest day. The concentrations of both mononitrates were lower on the exercise day, but the difference was already present before the exercise started.

Administration, Oral↗
PubMed1988

Pharmacokinetics of nisoldipine in renal dysfunction.

The pharmacokinetics of nisoldipine have been studied after oral administration of one 10 mg tablet to 3 groups of patients: Group A (n = 8) with a mean creatinine of 90 ml/min, Group B (n = 8) with a mean creatinine clearance of 12 ml/min and Group C of 12 patients on maintenance haemodialysis. All of them were studied off-dialysis and 7 were also studied on a dialysis day. No significant differences were observed between Groups A, B and C (on an interdialysis day) in AUC (0-7h), tmax, Cmax and plasma protein binding. Unchanged nisoldipine could not be recovered from the urine in any patient. Haemodialysis did not significantly affect AUC, tmax and Cmax, and nisoldipine could not be detected in the dialysate. The results indicate that the dose of nisoldipine need not be changed in patients with renal dysfunction, and that a supplementary dose is not required after haemodialysis. Blood pressure in the uraemics fell more than in the patients with good renal function.

Adult↗
PubMed1988

Testicular toxicity induced by single dosing of di- and mono-(2-ethylhexyl) phthalate in the rat.

The testicular toxicity of di-(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, and of its major metabolite, mono-(2-ethylhexyl) phthalate (MEHP), was assessed after a single dose in rats. Treatment with a single dose of 2.8 g/kg DEHP or 0.8 g/kg MEHP was sufficient to induce testicular atrophy as observed 7 days after dosing. Such a treatment had no effect on plasma FSH levels, and had varying effects on testicular zinc concentrations. After a single dose of 0.8 g/kg MEHP the testicular toxicity was age-dependent, in that only prepubertal rats were susceptible.

Animals↗
PubMed1988

Pharmacokinetics of organic nitrates in man: an overview.

The pharmacokinetics of glyceryl trinitrate are still not completely understood. The substance disappears rapidly from plasma largely by extrahepatic mechanisms. It is converted in glyceryl dinitrates and glyceryl mononitrates. After transdermal application of a controlled delivery system, plasma concentrations of glyceryl trinitrate can be maintained over the time period of application but, as for other routes, there are important intra- and inter-individual variations and fluctuations. Isosorbide dinitrate disappears less rapidly from the body; it is converted to the isosorbide mononitrates. Plasma concentrations of isosorbide dinitrate and mononitrates are quite predictable in different circumstances, e.g. on application of oral sustained release formulations. Measurement of the plasma concentrations of nitrates has been used to characterize different preparations and routes of administration. However, these plasma concentrations cannot be used to predict the effect, probably because of the important counter-regulation and tolerance which develop rapidly after administration of the drugs.

Absorption↗
PubMed1988

Study with positron emission tomography of the osmotic opening of the dog blood-brain barrier for quinidine and morphine.

A canine model was used to evaluate the possibilities offered by positron emission tomography (PET) for the study of drug distribution in the brain during altered states of the blood-brain barrier (BBB). PET was used to monitor the changes in the distribution of [11C]quinidine and [11C]morphine resulting from BBB-disruption by intracarotid infusion of a hyperosmolar mannitol solution. Injection of Evans blue dye allowing post-mortem evaluation of the degree of BBB-opening was used as a reference method. Brain radioactivity concentrations observed after i.v. injection of either [11C] quinidine or [11C]morphine were markedly increased by intracarotid mannitol infusion, whereas they were not affected by saline infusion. For both drugs a close correlation was found between the radioactivity concentrations and the degree of Evans blue staining within the brain hemispheres and within smaller regions of interest corresponding to quadrants of a hemisphere. This parallelism between the findings for radioactivity concentrations and Evans blue staining suggests that PET allows the detection of in-vivo changes in brain distribution of drugs resulting from alterations of the BBB permeability.

Animals↗