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Biomedical subjects

M B Regazzi

Publications and source records attributed to M B Regazzi.

At least 19 recordsLinked to original sources
PubMed1995

Modulation of all-trans retinoid acid pharmacokinetics in acute promyelocytic leukaemia by prolonged interferon-alpha therapy.

Continuous treatment with all-trans retinoid acid (ATRA) induces accelerated drug catabolism which is considered responsible for acquired resistance to ATRA. We studied the effect of interferon-alpha 2a (IFN) on ATRA pharmacokinetics in two patients with acute promyelocytic leukaemia (APL) in complete remission maintained by alternating 15 d of IFN and 15 d of ATRA. Day 15 ATRA levels obtained during IFN+ATRA treatment were significantly higher than those observed in patients maintained on ATRA alone. In one patient IFN was discontinued and day 15 ATRA levels decreased to those observed in patients scheduled for maintenance with ATRA alone. In our two patients IFN substantially reduced the induction of ATRA catabolism, indicating a potential role for IFN in modulating ATRA pharmacokinetics.

Drug Interactions↗
PubMed1995

Efficacy and pharmacokinetics of simvastatin in heart transplant recipients.

OBJECTIVE: To evaluate the efficacy and safety of simvastatin administered to a group of heart transplant patients receiving triple-drug immunosuppressive therapy. We also assessed the potential pharmacokinetic interaction between simvastatin and cyclosporine by comparing mean plasma concentrations of simvastatin beta-hydroxy acid, the major metabolite of the drug, in a group of heart transplant patients treated with cyclosporine and in a control group of patients who had not received heart transplants. Both groups received long-term (> 6 wk) simvastatin therapy. DESIGN: We monitored hyperlipidemia in 20 hypercholesterolemic heart transplant patients receiving simvastatin 10 mg/d and triple-drug immunosuppressive therapy. Changes in laboratory results before and after 4 months of simvastatin therapy were considered. The same laboratory data were monitored in a control group of 20 nonhypercholesterolemic heart transplant patients who were not treated with simvastatin but were receiving triple-drug immunosuppressive therapy. Plasma concentrations of simvastatin beta-hydroxy acid were measured in 14 hypercholesterolemic patients, 7 of whom had received heart transplants and 7 who had not. SETTING: The Division of Cardiology and the First Medical Clinic for the clinical study, as well as the Department of Pharmacology for the pharmacokinetic analysis. PARTICIPANTS: Forty heart transplant patients and 7 hypercholesterolemic nontransplant patients. MAIN OUTCOME MEASURES: Effectiveness of simvastatin was determined by comparing cholesterol and lipoprotein plasma concentrations in 20 patients who underwent heart transplant and were treated with simvastatin for 4 months. The safety of the drug was determined by analyzing changes in laboratory results in the treated group and in the control group, both those who had received heart transplants and those who had received immunosuppressive therapy. RESULTS: After 4 months of simvastatin therapy, total cholesterol decreased by 12.5% and low-density lipoprotein cholesterol decreased by 21.3%. The only statistically significant laboratory change was an increase of 28.7% in the alanine aminotransferase concentrations. Plasma concentrations of simvastatin beta-hydroxy acid were higher in heart transplant patients than in those who had not received heart transplants, the control group. CONCLUSIONS: Low-dosage simvastatin treatment seems to be safe and sufficiently effective to decrease cholesterol concentrations. Concomitant treatment with immunosuppressive therapy (primarily cyclosporine) in heart transplant patients appeared to cause a reduced metabolic clearance of simvastatin from the plasma. More extensive studies on the interaction between simvastatin and cyclosporine are needed to understand the marked variability found in the response to simvastatin.

Adult↗
PubMed1994

Busulfan.

OBJECTIVE: To review the current published studies evaluating the pharmacokinetics, clinical efficacy, safety, and toxicity of busulfan in pediatric and adult patients. DATA SOURCES: English-language literature published between 1953 and 1993 was analyzed; pertinent literature was reviewed. STUDY SELECTION: Emphasis was placed on pharmacologic studies and clinical trials involving busulfan therapy both in myeloproliferative disorders and in conditioning regimens for autologous or allogeneic bone marrow transplantation. DATA EXTRACTION: Data from both pediatric and adult studies were evaluated; emphasis was placed on the relationship between plasma concentrations of busulfan and its efficacy and toxicity. DATA SYNTHESIS: Busulfan has been used widely at conventional dosages (1-12 mg/d) for the treatment of patients with chronic myelogenous leukemia (CML). Busulfan at high doses (usually 16 mg/kg) given with other cytotoxic drugs (especially cyclophosphamide) is a common preparative regimen in patients undergoing allogeneic or autologous bone marrow transplantation (BMT) for acute or chronic leukemia and other nonmalignant disorders (e.g., hemoglobinopathies, inborn error of immune system, congenital metabolic disorders). Pharmacokinetics of high-dose busulfan are age-dependent. Busulfan systemic exposure and, thus, tissue and tumor exposure are lower in children than with adults. Relationships between toxicity (principally neutropenia, hepatic veno-occlusive disease, incidence of seizures) and drug exposure were found for busulfan. CONCLUSIONS: Busulfan is a useful, sufficiently safe drug in the treatment of patients with CML. At higher dosages, busulfan is a fundamental part of myeloablative therapies for patients undergoing BMT. As the pharmacokinetics and metabolism of busulfan is further understood, there is great potential for improving treatment outcome. An assessment of maximal tolerated exposure determined by therapeutic drug monitoring may decrease the incidence and lethality of regimen-related toxicities.

Age Factors↗
PubMed1992

Optimization of sampling time for cyclosporine monitoring in transplant patients.

Cyclosporine (CsA) dosing is based on CsA plasma or blood concentrations measured 12 to 24 hours after drug administration (trough levels). This study evaluated the relationship between the timing of CsA concentrations and subsequent pharmacokinetic parameters to predict an optimal sampling period. Plasma samples were obtained from 22 patients before their morning dose of CsA and at 2, 4, 6, 8, 10, and 12 hours after the dose on the 7th and on the 21st day after heart transplantation. The plasma samples were assayed by both HPLC and FPIA. The Cmax for CsA was achieved over a period ranging from 2 to 6 hours (mean/median = 4.7/4.0) during the day 7 and the day 21 studies. The mean (+/- SD) half-life was 3.2 (1.0) hours on day 7 and 2.9 (1.1) hours on day 21, (P > 0.05); the mean apparent oral clearance was 276 (117) L/hr on the day 7 and 269 (209) L/hr on day 21, (P > 0.05). When CsA plasma concentration by either FPIA and HPLC was monitored, the drug concentration best correlated with AUC was found to correspond to the plasma samples taken 4 to 8 hours after drug administration. The authors conclude that through blood sampling for therapeutic drug monitoring of CsA is not optimal, and that further studies are necessary to correlate concentration monitoring during the dosing interval with pharmacologic and toxicologic parameters.

Adolescent↗
PubMed1992

Pharmacokinetics of nicorandil in patients with normal and impaired renal function.

The pharmacokinetics of oral nicorandil 20 mg 12 hourly for 9 doses was evaluated in 21 hospitalized patients with angina pectoris due to coronary heart disease and with normal and impaired renal function. Patients were divided into 3 groups based on creatinine clearance (CLCr): GROUP I (n = 6) greater than 80 ml/min, GROUP II (n = 8) 20-80 ml/min, and GROUP III (n = 7) less than 20 ml/min. After the first dose, the total clearance of nicorandil (CL) value did not change with increasing renal failure and so was not dependent on creatine clearance. After the last dose CL was 51 l.h-1 in Group I, 44 l.h-1 in Group II and 56 l.h-1 in Group III, and it was not related to creatinine clearance. The percentage of the dose excreted in the urine was 0.4%. No significant difference was noted in any of the other pharmacokinetic parameters examined in the three groups, not even on comparing values obtained on the first and last days of treatment. The findings suggest that there is no need to change the dose of nicorandil in subjects with different degrees of renal failure.

Administration, Oral↗
PubMed1992

Pharmacokinetics of ofloxacin in elderly patients and in healthy young subjects.

The pharmacokinetics of ofloxacin, a fluoroquinolone widely used in the treatment of bacterial infections, may be different according to age, owing to the biological differences that exist between an elderly organism and a young subject, especially as regards the renal and the hepatic function. In our study the pharmacokinetics of ofloxacin in 12 elderly patients was found to be different from those of 12 healthy young volunteers. The elimination half-life (t1/2) was slightly shorter in the young subjects than in the elderly: 6.2 (0.9)h against 8.5(1.2)h respectively. The oral total clearance was lower in the geriatric patients compared to the young healthy volunteers: 83.3(16.6) ml/min in the first group, and 23.3(33.3) ml/min in the second group. AUC and peak plasma concentration in elderly exceeded those noted in young healthy volunteers. The results of this study suggest that, compared with younger subjects, older patients experience delayed elimination of ofloxacin. It would be reasonable, from a pharmacokinetic point of view, to limit the dose of ofloxacin in patients more than 75 years old, at least to one half of that given to younger patients.

Administration, Oral↗
PubMed1992

[The bioavailability of nicorandil after oral administration of a single dose of 10 or 20 mg preparations].

To evaluate the bioavailability of 4 different formulations of nicorandil, 10 mg and 20 mg (Bracco) versus 10 mg ang 20 mg (Merck), we have carried out a study involving 24 young healthy volunteers. The drug was administered in single oral dose and the plasma concentration levels were evaluated by HPLC method. From the results obtained, we have seen that both the 2 products of 10 mg (A and B) and the 2 products of 20 mg (C and D) are equivalent and have high relative bioavailability: it reaches the values of 96.5% (A versus B) and 120% (C versus D). As regards the 2 formulation of 20 mg, the results of bioavailability are confirmed by data obtained from dissolution study in vitro, where the dissolution is almost complete in 30 minutes.

Adult↗
PubMed1991

The effect of aging on the pharmacokinetics of nizatidine.

A single oral dose of 300 mg of nizatidine was administered to two groups of volunteers: a first group of 12 young healthy subjects and a second group of 12 elderly patients, in order to compare the pharmacokinetic parameters and to verify a possible influence of the age on nizatidine's kinetics. Blood samples were collected periodically and plasma concentrations of the drug were determined by a specific HPLC method. The results evidenced differences among the pharmacokinetic parameters of the two groups: the mean of Cmax was higher in the elderly than in the young (3.28 mg/ml against 2.23 mg/ml), the peak time was prolonged in the elderly (2.1 h against 1.00 h) and the AUC values were higher too (12.17 in the elderly and 7.99 in the young). Only the elimination half-life t1/2 was slightly higher in the elderly (1.8 h against 1.7 h in the young).

Adult↗
PubMed1991

Pharmacokinetics of omeprazole in cirrhotic patients.

Omeprazole (CAS 73590-58-6), an H+, K+ ATPase inhibitor, is a potent suppressor of gastric acid secretion and a very active substance in the treatment of duodenal and gastric ulcers. The kinetic profile of omeprazole is well defined for healthy volunteers and for some high-risk population, but not so far for patients with liver disease. As the substance is mainly metabolized in the liver, changes in liver circulation and/or function might lead to changes in the pharmacokinetics of omeprazole. Aim of the study was to evaluate the kinetic profile in patients with liver disease and compare the results obtained in healthy volunteers, 16 subjects were included in the study: 8 patients with liver cirrhosis and 8 healthy volunteers. A single oral dose of omeprazole 20 mg was administered: plasma samples were collected for 24 h since omeprazole administration. The principal pharmacokinetic parameters were estimated for the two studied populations.

Adult↗
PubMed1990

Measurement of cyclosporine in plasma of cardiac allograft recipients by fluorescence polarization immunoassay.

The Abbott TDx fluorescence polarization immunoassay (FPIA) procedure for measuring cyclosporine A (CsA) was evaluated and compared with the Sandoz polyclonal radioimmunoassay (CsA RIA kit) method. This drug assay was evaluated for precision, calibration, stability, and accuracy. Within-run precision studies utilizing 25 replicate analyses of the three control preparations (containing CsA in the 60-800 ng/ml range) resulted in coefficients of variation (CV) ranging from 1.0 to 9.1%. The CVs of between-run precision determined by assaying the same control drug levels for five consecutive working days ranged from 3.9 to 4.6%. Calibration curve stability was assessed by examining the drift in control values over a 2-week period. Maximum plasma ranged from 82.6 to 108.2%. Four hundred plasma samples were obtained from 30 heart-transplant patients during the first 6 months of CsA therapy and each sample was analyzed simultaneously by TDx and RIA. Linear regression analysis of the results obtained for each patient (x = RIA, y = FPIA) revealed the following mean values: r = 0.87, (CV = 13.7%), slope = 1.47 (CV = 39.2%). Moreover, the concentration of CsA was determined in 35 patient samples both by TDx and high-performance liquid chromatography (HPLC). FPIA results up to 12 times higher than HPLC results have been noted.

Chromatography, High Pressure Liquid↗
PubMed1989

Bioequivalency of three tableted gallopamil products.

A three cross-study was conducted in 12 healthy male volunteers to evaluate the relative bioavailability of three different gallopamil tablets: Product A-Galcan 25 mg, Product B-Galcan 50 mg and Product C-Procorum 50 mg. Each dose was administered as a single tablet after an overnight fast, and blood samples were obtained for 12 hours. There was no statistically significant differences among the three products for the mean area under the plasma concentration-time curves (when corrected for the different doses). The relative bioavailability of Product A and B to Product C was respectively 96.3% (ESM = 12.4%) and 103.1% (ESM = 10.2%). Statistically significant (p less than 0.05) differences were found in Tmax between Product C (1.0 hr) and both Product A (2.1 hr) and Product B (2.4 hr). A longer-lasting absorption should always diminish peak to trough fluctuations during multiple dosing and to this extent Product B has some advantage over Product C.

Adult↗
PubMed1988

Comparison of the effectiveness of dihydroquinidine and quinidine on ventricular ectopy after acute and chronic administration.

The aim of this study was to compare the pharmacokinetics and antiarrhythmic activity of dihydroquinidine and quinidine in 14 patients (11 men, 3 women, aged 28 to 67 years) with heart disease and chronic, stable, high-frequency premature ventricular beats (PVB) (greater than 100/hr). A randomized, double-blind, crossover, placebo-controlled protocol was utilized. During Holter monitoring the patients were given either dihydroquinidine or quinidine as the gluconates in an oral solution (600 mg); blood samples were taken 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours later. The patients were then assigned to three successive treatment periods of 7 days each: dihydroquinidine HCl (900 mg/day), quinidine polygalacturonate (1,650 mg/day), or placebo. At the end of each period 24-hour Holter monitoring was carried out and a blood sample was taken for determination of drug concentration. By comparing the area under the curves dihydroquinidine was 59% as available as quinidine; rates of absorption and elimination were similar. Mean peak blood levels of dihydroquinidine and quinidine were 1.06 +/- 0.34 and 2.15 +/- 0.96 micrograms/ml, respectively. After dihydroquinidine, eight patients had a positive response (greater than 50% reduction in PVB frequency), while seven patients responded to quinidine. During maintenance treatment both dihydroquinidine (233 +/- 330) and quinidine (234 +/- 311) reduced the mean PVB frequency per hour compared to placebo (690 +/- 569). Nine patients (64%) on dihydroquinidine and eight (57%) on quinidine had greater than 70% decrease in mean PVB frequency per hour. Steady-state peak plasma concentrations of dihydroquinidine and quinidine were 1.10 +/- 0.41 and 2.24 +/- 1.13 micrograms/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

A theophylline dosage regimen which reduces round-the-clock variations in plasma concentrations resulting from diurnal pharmacokinetic variation.

Slower drug absorption at night can leave residual drug from an evening dose of a sustained-release product remaining to be absorbed at the time of the next morning's dose, thereby giving higher plasma concentrations of the drug during the day than the night. When a capsule product releasing theophylline over 12 h after a morning dose was given repetitively at 8 a.m. and 8 p.m. for 4 days, daytime plasma concentrations from 4 h to 8 h after the dose were about 40% greater than corresponding night-time concentrations, and the mean steady-state concentration during the night-time interval was only 81% of that during the daytime interval. Altering the regimen to one capsule at 12 noon and one at 10 p.m. eliminated all significant differences between a.m. and corresponding p.m. plasma concentrations of theophylline and between the mean steady-state concentrations for each of the interdose intervals within a day.

Adult↗
PubMed1986

Ceftazidime in the treatment of Pseudomonas infections in intensive-care patients.

The present study was designed to define the clinical activity and pharmacokinetics of ceftazidime in Pseudomonas sp. infections. The intensive care patients included in this study were hospitalized for at least 2 weeks and have frequently received antibiotic treatment which contributed with poor host resistance to the infections with highly resistant Pseudomonas strains. Sixteen adult patients entered the study. Their age ranged from 18 to 70 years. Ceftazidime was administered in a dose of 2 g three times daily by a constant infusion over 20-30 min. Frequent clinical assessment multiple cultures and determination of renal, hepatic and bacteriological functions were performed. Bacterial cultures were obtained prior to the beginning of therapy and every 2-3 days thereafter with a follow-up period of about 1-2 weeks. Pharmacokinetics in the blood were performed. Measurements of ceftazidime were made by using HPLC. Mean peak serum concentration of ceftazidime was 58.5 micrograms/ml after administration of 2.0 g of ceftazidime and eight hours after dosing the mean plasma concentration was about 5 micrograms/ml. No accumulation of ceftazidime could be observed during the treatment period. Mean plasma half-life was 2.1 hours at the beginning and 2.2 hours at the end of therapy. The mean apparent volume distribution was 0.35 l/kg. No severe adverse effects were reported throughout the study. Ceftazidime may be effectively used as single antiinfective agent in various conditions and higher plasma concentrations are an important predictor of bacteriological and clinical response in pulmonary infections caused by Pseudomonas species.

Adolescent↗
PubMed1985

[Bioavailability of a delayed-action aminophylline preparation].

Absorption of theophylline from one commercial product labelled as aminophylline sustained release was compared to the absorption from an oral solution of aminophylline in a single-dose bioavailability study. Aminomal-R tablets had bioavailability (101.2 +/- 19) statistically indistinguishable from that of the standard but showed significantly slower absorption (peak times of 3.6 +/- 1.1 h vs 1.3 +/- 0.8 h) and lower peak plasma concentrations (16.8 +/- 4.7 mg/l/1 g aminoph. dose vs 21.1 +/- 4.2 mg/l/1 g aminoph. dose). Projections of plasma concentrations upon multiple dosing were made from single dose data: the dosage interval (every 12 h) concentration ratio which reflects both the frequency of dosing and the entry of the drug into and removal from the body was of 1.8 vs 3.1.

Administration, Oral↗