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Biomedical subjects

R L Galeazzi

Publications and source records attributed to R L Galeazzi.

At least 55 records · Page 3Linked to original sources
PubMed1984

Single dose pharmacokinetics of mabuterol in man.

The pharmacokinetics of 1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butylamino-ethanol hydrochloride (mabuterol), a new bronchodilator in the series of phenyl-ethanolamine derivatives, was investigated in six healthy young male volunteers. Use of tritiated compound allowed characterization of the plasma concentration-time profile of unchanged drug after a single oral dose of 40 micrograms in the form of a drinking solution. Peak concentrations of 96-160 pg/ml were reached between 1.5 and 3.2 h and drug concentrations declined thereafter in a biphasic pattern. Elimination of unchanged drug was slow (t 1/2 beta 20-30 h) due to a low clearance (CL/F 3.0 ml/min/kg) and a large volume of distribution (V beta/F 5.8 l/kg). Absorption of the drug from the gastrointestinal tract was complete and availability of unchanged drug to the systemic circulation could be estimated (F greater than 0.91) using flow model concepts. At peak concentrations mabuterol accounted for only 46% of total radioactivity in plasma but no major conjugated or unconjugated metabolite has been identified. The active tert.-butanol-amino-metabolite was present in negligible amounts (less than 10 pg/ml). The time profile of total radioactivity in plasma closely resembled that reported for structurally related compounds. Excretion of total radioactivity was mainly renal (80% of dose) but the fraction of the dose eliminated unchanged in urine was only 24%. Fecal excretion was low with a cumulative amount recovered over the entire study period of 3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1983

[Drug therapy in impaired liver and kidney function].

In patients with impaired renal function the indication for a given drug, the dose and the risk of unwanted effects are altered. With simple mathematical tools, the "a priori" dose can be quantitatively adjusted to the existing renal function. However, for changes in the indications for a given drug and for checks on the effects of pharmacotherapy, only a qualitative approach is possible. In the presence of hepatic failure the same rules generally apply, though in this case no quantitative rule for reduction of the "a priori" dose can be given.

Biological Availability↗
PubMed1983

Continuous infusion of high-dose metoclopramide for the prevention of nausea and vomiting in patients receiving cancer chemotherapy.

Fourteen patients undergoing strongly emetic cancer chemotherapy received a total of 33 continuous infusions of high-dose metoclopramide to prevent nausea and vomiting. Metoclopramide 2 mg/kg was given as an i.v. infusion over 15 min followed by continuous infusion over 13 h of 5 mg/kg. The antiemetic response could be evaluated in 12 patients receiving their first continuous metoclopramide infusion. Six patients were partly or completely protected from acute gastrointestinal disturbances. Three patients experienced a short-lived extrapyramidal syndrome during the continuous metoclopramide infusions. Other side effects observed were mild. Thus, high-dose metoclopramide given as a continuous infusion is an effective antiemetic treatment in patients receiving cancer chemotherapy.

Adult↗
PubMed1983

Serum concentrations of amiodarone during long term therapy. Relation to dose, efficacy and toxicity.

In 17 patients on long term therapy with amiodarone, serum drug levels measured by HPLC were related to pharmacological effects. At steady state, serum levels were directly proportional to the dose, 5 mg/kg per day leading to an average serum level of approximately 2.5 mumol/l. The non-amiodarone level of iodine averaged 4-times higher than the level of amiodarone iodine. The elimination half-life of amiodarone ranged from 21 to 78 days, and of non-amiodarone iodine from 24 to 160 days. Control of arrhythmias was satisfactory in all 12 evaluable patients, when the serum amiodarone level exceeded 1.5 mumol/l. Deterioration of vision and polyserositis occurred only at amiodarone levels above 4 mumol/l. Tentatively, a therapeutic range of 1.5 to 4 mumol/l is proposed. In contrast, thyroid dysfunction was observed at any amiodarone level. In view of the narrow therapeutic window, therapy with amiodarone may be optimized by monitoring its serum level and in addition, thyroid function should be regularly checked.

Adult↗
PubMed1983

Constant kinetics and constant concentration-effect relationship during long-term beta-blockade with pindolol.

Long-term beta-blockade is said to increase the number of beta-receptors. The effect of beta-blockers could therefore be reduced after long use. We tested this hypothesis in nine healthy subjects given 15 mg pindolol daily for 4 wk. Plasma concentrations (measured fluorometrically), isoproterenol dose-response relationship (to calculate the dose needed to increase heart rate by 25 bpm), renin, epinephrine, and norepinephrine were measured several times before and after the first and last dose. Kinetic parameters remained stable: total clearance (Cltot) = 45.2 and 42.9 l/hr, and Vdss = 205.8 and 198.6 l after the first and last dose. The concentration-effect relationship, plotted as the "dose ratio minus one" against the log of the plasma concentration was identical after 4 wk. Basal plasma renin activity was reduced slightly and the increase of stimulated plasma renin was blunted by pindolol even after 4 wk. The initial lowering of unstimulated renin by pindolol in the first 2 hr after dosing was not detectable after 4 wk. Epinephrine and norepinephrine levels in plasma were not changed initially nor after 4 wk. It is concluded that pindolol has a stable kinetic profile over time and that its beta-blockade does not induce tachyphylaxis.

Adult↗
PubMed1983

Plasma isosorbide dinitrate concentrations and effect after chewable and high-dose, sustained-release formulations.

Isosorbide dinitrate (ISDN) was given to eight healthy volunteers either as 5 mg chewable ISDN hourly or as 40-mg, slow-release formulation every 8 h. Plasma concentration of ISDN and its two metabolites were measured during one dosing interval at steady state. Mean steady-state plasma concentration (Cpss) during the interval was taken as a measure for bioavailability. Cpss after bucal absorption was similar to that after the sustained-release preparation. Relative bioavailability of the latter reached 111%. The effect of ISDN was measured by digital plethysmography (DPG) during the first dosing interval and after 10 and 48 h, when a steady state had been reached with each formulation. DPG changes were of similar magnitude during the first 10 h, but showed a 30% decrease after 48 h. This tolerance is probably due to physiologic counterregulation. Changes in DPG reflect effects of ISDN which can be used during short-term application of the drug to assess systemic bioavailability. Development of tolerance, however, precludes the use of DPG to assess bioavailability in long-lasting steady-state experiments.

Adult↗
PubMed1982

Levonantradol, a new antiemetic with a high rate of side-effects for the prevention of nausea and vomiting in patients receiving cancer chemotherapy.

Levonantradol, a new antiemetic compound pharmacologically related to the cannabinoids, was given to 17 patients who had experienced severe and protracted nausea and vomiting during previous courses of cancer chemotherapy, and to six patients receiving a first course of strongly emetic cytostatic treatment. Eight patients were partially protected from acute gastrointestinal disturbances. Of the 23 patients, 21 exhibited some toxicity, with six patients exhibiting major affective side-effects and 13 patients complaining of pain at the injection site. Levonantradol is an active antiemetic compound. Due to the rate of side-effects observed in our study however, we would not recommend use of this agent as an antiemetic drug.

Adult↗
PubMed1982

Pharmacokinetics of intravenous isosorbide-dinitrate.

The kinetics of isosorbide dinitrate (ISDN) after i.v. administration and the absolute availability of an oral slow release preparation (SR) were studied in young healthy volunteers. ISDN and the 2- and 5-mononitrates of isosorbide (2-MN, 5-MN) were determined by GLC. After i.v. administration plasma levels of ISDN declined biexponentially and could be adequately described by an open two compartment body model. Distribution half-life was extremely rapid (2-5 min). Terminal disappearance had a half-life of 67 (62-75) min (mean, range). Total plasma clearance was 1.6 (1.2-2.2) litres X min-1, thus approaching liver blood flow. Nevertheless, absolute systemic availability (F) or oral ISDN amounted to 22% (16-29%). Assuming that oral ISDN is completely absorbed and blood levels do not exceed serum levels, an upper limit of hepatic clearance (liver blood flow 1.5 litres X min-1 X (1-F/100)) can be estimated, which is significantly smaller (p less than 0.05) than the measured clearance. This finding is best interpreted by assuming that ISDN is partly eliminated by extrahepatic routes, which is further substantiated by a different pattern of metabolites after i.v. and oral dosing. Whereas after i.v. administration more 2-MN is produced, 5-MN is the main metabolite after oral ISDN. Since the glutathione-S-transferases are found in the cytosol of most cells, it seems likely that other organs than the liver contribute to the metabolism of ISDN.

Administration, Oral↗
PubMed1982

Erythrocyte deformability in dialysed and non-dialysed uraemic patients.

In thirty-one uraemic patients, fourteen on conservative treatment and seventeen on long-term haemodialysis, erythrocyte deformability, measured as filtration half-time in a paper filtration experiment, was studied. The two groups were comparable concerning age, sex and kidney disease. Although the mean filtration half-time for erythrocyte suspensions was normal in non-dialysed patients there was a positive linear correlation (P less than 0.01) between serum creatinine and filtration half-time in this group. Filtration half-time was increased in dialysed patients, indicating impaired deformability in the latter (P less than 0.001). Filtration half-time showed a good inverse correlation with the packed red cell volume in the non-dialysed (P less than 0.001) and in the dialysed group (P less than 0.01). As pre- and post-dialysis filtration half-times were the same, it appeared that the more severe uraemic state of dialysed patients was responsible for the impairment of erythrocyte deformability and not the dialysis procedure itself.

Adult↗
PubMed1982

Pharmacokinetics of oxytetracycline and therapeutic implications in veal calves.

Pharmacokinetic parameters of oxytetracycline were analysed in healthy preruminant veal calves after intravenous, intramuscular and oral administration. The serum half-lives in the beta-elimination phase of both 10% and 20% solutions after i.v. injection of 10 mg/kg were similar (7.07 +/- 1.36 h and 7.16 +/- 1.17 h, mean +/- SD), whereas the total body clearance and the apparent volume of distribution were higher for the 20% solution. Serum concentrations above 0.5 microgram/ml were maintained with both formulations during 12-24 h but were only above 4 micrograms/ml to 5 h. Intramuscular administration of the 20% solution gave a complete absorption with two rate constants of absorption, a faster (t1/2 alpha 1 = 0.27 h) and a slower one (t1/2 alpha 2 = 10.90 h) responsible for the delayed elimination half-life after this route of application (t1/2 beta = 9.83 +/- 1.35 h). Mean serum concentrations reached a maximum level of 3.01 +/- 0.72 micrograms/ml at 4.01 +/- 2.84 h and decreased to 0.5 microgram/ml between 12 and 24 h. 50 mg/kg given orally with a milk replacer were found to have a mean bioavailability of 46.35%. A mean serum peak level of 4.99 +/- 1.37 micrograms/ml was achieved at 9.16 +/- 1.99 h and the mean concentration was still above 0.5 microgram/ml after 48 h. The elimination half-life (t1/2 beta = 10.66 +/- 3.15 h) reflected the slow absorption step (t1/2 alpha 2 = 10.15 h) following that responsible for the initial faster absorption (t1/2 alpha 1 = 1.99 h). Comparison of the area under the serum curves gave mean values of 117% for tetracycline and of 53% for chlortetracycline relative to oxytetracycline (arbitrarily fixed at 100%) after identical oral dosage of the three tetracyclines. We also propose and discuss a dosage schedule based on minimal inhibitory concentrations of different susceptible pathogens.

Administration, Oral↗
PubMed1982

Dyspnea proneness to CO2 stimulation and personality (neuroticism, extraversion, MMPI factors).

The relationship between extroversion (E), MMPI factors on the one hand and the ventilatory response to CO2 on the other was examined in order to extend and clarify earlier studies. 30 male nonsmokers were studied using the method of Read (delta VE/PaCO2 as index of readiness to react with dyspnea upon CO2 stimulation). Extroversion (E) and neuroticism (N) was assessed by the Eysenck Personality Test. The panic-fear (PF) and the ego-strength (Es) scales were extracted from the MMPI. The correlation between E, N, MMPI values and delta VE/PaCO2 was measured with Pearson's correlation. Reliability between the first and second respiratory test was obvious, r = 0.66 (p less than 0.001). The correlation between the psychological parameters and the readiness to respond to CO2 was very low in the first test. In the second test, the r for hypochondriasis, depression and PF was 0.25, 0.28 and 0.29, respectively (p less than 0.1; 2-tailed), for N the r was 0.33, for psychastheny 0.33, and for Es -0.40 (all p less than 0.05). In agreement with Saunders and co-workers, we found no correlation for E. Our results indicate that readiness to react to CO2 is related to anxiety (positive correlations for N, Hs, Pt and PF, and negative for Es). This corresponds to clinical observations.

Adult↗
PubMed1981

[The determination of drug blood levels: when? which?].

Blood levels of drugs are easy to prescribe but remain difficult to interpret. They are almost useless if pharmacologic effects are measurable. Indications for measurement of blood levels are absence of measurable effects, narrow therapeutic margin, anticipated changes in pharmacokinetics or lack of response. For the interpretation of the results of such determinations a knowledge of at least some basic principles in pharmacology and kinetics is necessary.

Dose-Response Relationship, Drug↗
PubMed1981

N-Acetyl-procainamide kinetics in the elderly.

Plasma and saliva N-acetyl-procainamide (NAPA) concentrations were measured by high-power liquid chromatography (HPLC) after intravenous infusion of 750 mg to 14 elderly patients (x age = 69 yr). The plasma NAPA disappearance curve can best be described by a two-compartment body model. Mean total body clearance was 10.6 1/hr, Vdss 125.8 1, and terminal half-life (t 1/2) 8.8 hr. A nonrenal clearance of 2.72 1/hr was calculated, that is, 19% of the expected total body clearance with normal kidney function. Saliva concentrations show huge inter- and intraindividual variability and are probably not usable for NAPA monitoring in older patients.

Acecainide↗
PubMed1980

[Steady-state plasma and saliva concentrations of procainamide and N-acetyl-procainamide after a sustained release preparation].

With ordinary procainamide tablets a dosing interval of 3-4 hours must be chosen to achieve therapeutically useful plasma concentrations during the entire interval. The concentrations of procainamide and its N-acetylated metabolite, NAPA, have been studied in the plasma of 10 normal volunteers and 11 patients who were given a new sustained release preparation at 8 hour intervals. Blood samples were taken between two doses on the fourth day of treatment. Procainamide showed levels within the accepted therapeutic range during the entire dosing interval. A dose of 4.5 g per day per 70 kg body-weight is necessary in order to achieve adequate levels. NAPA concentrations did not fluctuate during the dosing interval and mean steady-state concentrations were influenced predominantly by the degree of renal function. Saliva to plasma concentration ratio, measured in four patients, showed huge inter- and intraindividual variability. Therefore, saliva concentrations measurements of procainamide and NAPA are of little clinical use.

Acecainide↗