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Biomedical subjects

R J Royer

Publications and source records attributed to R J Royer.

At least 37 records · Page 2Linked to original sources
PubMed1989

Role of ancillary properties of beta-adrenoceptor antagonists in protecting the heart from anoxia.

The mechanism of the cardioprotective action of beta-blocking drugs against anoxia or ischemia is still not clear. We used beta-blockers (5 x 10(-7) M) of various pharmacodynamic profiles in a model of isolated, perfused working guinea pig heart subjected to 20 min of anoxia to study this. The cardioprotective effects were evaluated by measuring the recovery of the flow indices after 15 min of reoxygenation. There was a significant cardioprotective action (as measured by the effect on stroke volume recovery and on recovery of other flow and work indices) of the beta-blocking properties (nadolol, P less than 0.05), of the membrane-stabilizing property [+)-propranolol, P less than 0.05) and of a combination of these two properties with (+/-)-propranolol, which had a significantly greater effect than nadolol (P less than 0.05). The addition of weak (acebutolol) or strong (pindolol) intrinsic partial agonist activity had no clear unfavourable effect, as the degree of cardioprotection was comparable with that obtained with (+/-)-propranolol. The stroke volume recovery (percent recovery after anoxia) in the control hearts was 42.57 +/- 12.75 compared to 54.84 +/- 6.94 in hearts pretreated with nadolol, 62.99 +/- 11.41 with (+)-propranolol, 71.02 +/- 11.36 with (+/-)-propranolol, 72.63 +/- 13.08 with acebutolol and 68.01 +/- 15.42 with pindolol. In vitro heart protection from anoxia with beta-blockers would appear to be related to beta-blocking activity and/or membrane stabilizing property but not a function of partial agonist activity. These ancillary properties of beta-blockers should thus be taken into account in studies on cardioprotection.

Adrenergic beta-Antagonists↗
PubMed1989

Clinical pharmacokinetics of nonsteroidal anti-inflammatory drugs in the cerebrospinal fluid.

The pharmacokinetics of nonsteroidal anti-inflammatory drugs (NSAIDs) in the cerebrospinal fluid (CSF) is of clinical interest as it may be related to some of their properties and side-effects. Two types of NSAIDs can be described with respect to their concentration and time course in CSF: in the first type, the transfer across the blood-brain barrier seems to be controlled by simple physico-chemical factors. These drugs (oxyphenbutazone, indomethacin, ketoprofen) are characterized by a high lipophilicity. At steady state, their free plasma concentrations correspond to their CSF concentrations. The second group consists of more hydrophilic compounds (salicylates); there is no correlation between plasma concentrations and CSF concentration. Further investigation needs to be carried out on CNS side-effects and the antialgesic activity of salicylates in relation on their CSF distribution.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

Tianeptine and its main metabolite pharmacokinetics in chronic alcoholism and cirrhosis.

The effect of chronic alcoholism (with or without associated moderate cirrhosis) on the disposition of the antidepressant tianeptine, which is devoid of substantial first-pass metabolism, was examined in 21 patients and 11 age-matched controls. Pharmacokinetic parameters for tianeptine and its C5 acid analogue metabolite (MC5 metabolite) were estimated by non-compartmental analysis. The area under the curve (AUC) for tianeptine, following a 12.5mg single oral dose, was decreased by 31% in chronic alcoholics and increased by only 14% in cirrhotics, compared to controls. These changes did not attain statistical significance. The trend of changes in the AUC for the MC5 metabolite was similar to that observed for the parent drug. No statistical difference was found in the terminal half-life for both tianeptine and its MC5 metabolite between patients and controls. On the basis of this study, it appears unnecessary to modify the proposed dosage regimen used in clinical trials (tianeptine sodium salt 12.5mg 3 times daily) in chronic alcoholics with or without associated moderate cirrhosis.

Adult↗
PubMed1989

[Mechanisms of undesirable effects of drugs].

Better prevention against adverse drug reactions could be obtained by improving our knowledge of pathological mechanisms and particularly risk factors. Because it is a medical act, the diagnosis must be made by a clinician who must then report it to his Drug Control Center.

Dose-Response Relationship, Drug↗
PubMed1988

The effect of food on the systemic availability of ketoprofen.

We have studied the pharmacokinetics of ketoprofen, a non-steroidal anti-inflammatory drug, in 12 patients after a single 100 mg oral dose both in fasting conditions and with a meal. Food significantly affected the peak plasma concentration of ketoprofen and decreased its absorption rate. However, the extent of absorption of ketoprofen, as reflected by the area under the plasma concentration time curve, appeared to be unchanged in the presence of food.

Administration, Oral↗
PubMed1988

Pharmacokinetic and metabolic parameters of tianeptine in healthy volunteers and in populations with risk factors.

Following oral administration in the fasting healthy subject, the mean maximum concentration of tianeptine is 334 +/- 79 ng/ml. Absorption of tianeptine from the tablet form is rapid and complete. Maximum plasma concentration is obtained by the first hour following administration (0.94 +/- 0.47 h). Absolute bioavailability is 99 +/- 29%. Tianeptine is thus rapidly and completely absorbed in the tablet form and is not subject to first-pass effect. Distribution of tianeptine in the body is characterized by the following: its rapidity, the mean distribution half-life being about 0.7 h; its limited extent, the apparent volume of distribution being about 0.8 L/kg (0.77 +/- 0.31 L/kg); and protein binding, which averages 93.8 +/- 2.4%. Elimination of tianeptine is characterized by a short mean half-life of 2 h 30 min (2.5 +/- 1.1 h) and by renal excretion of 0.4 ml/min (0.4 +/- 0.4 ml/min). Tianeptine is extensively metabolized. Major metabolites are analogs of tianeptine with a C5 and C3 lateral chain and a N-demethylated derivative. Studies have shown negligible influence on pharmacokinetic parameters of chronic alcoholism even in case of hepatic cirrhosis. In renal failure, and in the elderly, studies have revealed a 1-h prolongation of elimination half-life which suggests that the dosage should be limited to two tablets per day in such cases.

Administration, Oral↗
PubMed1987

Total and free ketoprofen in serum and synovial fluid after intramuscular injection.

Free and total ketoprofen levels in serum and synovial fluid were determined in 37 patients after a single intramuscular injection of ketoprofen, 100 mg. Free drug was separated by equilibrium dialysis. Ketoprofen was assayed by HPLC. Ketoprofen penetrated into the joints rapidly and significant concentrations were found at 15 minutes. The equilibrium time was about 3 1/2 hours. The AUC for total ketoprofen was greater in serum than in synovial fluid. On the other hand, the free fraction AUC in the serum and synovial fluid were quite similar. The mean residence time in the joint was about three times that in the systemic circulation. Ketoprofen was strongly bound to proteins and the percentage of free ketoprofen was not significantly different between serum and synovial fluid. These results provide a possible explanation for duration of the therapeutic effect of ketoprofen despite the short elimination half-life from the serum.

Adolescent↗
PubMed1987

Conversion from intravenous to oral slow-release disopyramide in acute myocardial infarction.

Twelve patients with acute myocardial infarction were given 1.5 mg/kg/5 min bolus +0.4 mg/kg/hr 6 hr IV infusion of disopyramide followed by 250 mg twice daily of a slow-release oral formulation of this drug. Plasma concentrations of total disopyramide rapidly reached steady-state within the therapeutic margins. The plasma steady-state concentrations of the major metabolite mono-N-dealkyl-disopyramide (MND) showed large intra-individual variations. There was no correlation between plasma levels of either disopyramide or MND and the occurrence of anticholinergic side effects. The drug had no significant effect on mean blood pressure, heart rate, or ECG intervals. This therapeutic regimen, including conversion from the IV form to oral slow-release tablets, could be recommended in myocardial infarction.

Adult↗
PubMed1986

[Clinical evaluation of drugs in chronic cardiac failure].

As the acute complications of cardiovascular diseases are better controlled, the number of patients with chronic heart failure will no doubt increase, together with the need for new treatments of this condition. The effectiveness of these new drugs on the heart function and on the patient's functional status, quality of life and survival must be assessed by very strict evaluation methods. Evaluating the cardiac function requires haemodynamic investigations by proven techniques. Even when taken globally, the haemodynamic values do not always provide information on the patient's clinical and functional status which must therefore be assessed separately, using specific methods. The exercise load, duration and oxygen peripheral consumption measured by established techniques are, in fact, the variables best correlated with the patient's functional status. The effects of drugs must be evaluated at rest and during exercise, but also in short and long term, with a systematic search for tachyphylaxis. Improvements in much less than quality of life much greater than and tolerance of treatment can be evaluated by appropriate questionnaires filled in by the patients. Assessing the effect of any treatment on survival of cardiac patients is always difficult. It requires epidemiological studies which are invariably delicate and costly but cannot be avoided for such an important matter.

Clinical Trials as Topic↗
PubMed1986

Estimation by high-performance liquid chromatography of ketoprofen in plasma. Application to the study of its protein binding.

A method of estimation by high-performance liquid chromatography of ketoprofen in plasma is proposed. This method is rapid, simple, and very sensitive: it allows concentrations of 2 ng/ml to be determined. The internal standard is (benzoyl-4-phenyl)-2-butyric acid. The drug is extracted from a biological fluid in ether, which is then evaporated; the residue is taken up in chromatographic eluant (acetonitrile/phosphate buffer pH 7), analysed by reverse-phase chromatography and detected by spectrophotometry at 256 nm. In spite of the very strong protein binding of this drug, this method allowed the determination of its free concentration in plasma.

Carrier Proteins↗
PubMed1985

Diffusion of intramuscular ketoprofen into the cerebrospinal fluid.

Serum and cerebrospinal fluid (CSF) concentrations of ketoprofen have been measured in 36 patients hospitalised for sciatica. Diagnostic lumbar puncture was done 15 min to 13 h after a single 100 mg intramuscular dose of ketoprofen. Serum and CSF were sampled at the same time. Free serum concentrations were determined by equilibrium dialysis. Total and free concentrations were assayed by a highly sensitive and specific HPLC method. Ketoprofen rapidly crossed the blood-brain barrier and was detected in CSF 15 min after its administration. The rapid diffusion can be explained by the high lipid solubility of the drug. The CSF level was in equilibrium with the free serum concentration from the second to the 13th hours.

Adult↗