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M B Regazzi

Publications and source records attributed to M B Regazzi.

68 records · Page 4Linked to original sources
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↗
PubMed1984

Pharmacokinetics and clinical efficacy of indomethacin in premature infants with patent ductus arteriosus.

Despite a considerable amount of investigation, controversy continues concerning the use of indomethacin in inducing the closure of patent ductus arteriosus. This controversy may be attributable to differences in dosage, route of administration, postnatal age at treatment and the variable pharmacokinetics of the drug in premature infants. The pharmacokinetics and clinical efficacy of i.v. administered indomethacin in five premature infants with PDA were evaluated. There was considerable intersubject variability in the half life of elimination (63.1 +/- 38 h). This variability was mainly due to clearance (0.0086 +/- 0.0069 l/h/kg) rather than to distribution volume variability (0.54 +/- 0.27 l/kg). A reduction of half life was observed after the second dose, probably due to a maturation process. A permanent closure of the ductus was obtained in two patients after the first dose and in two patients after the second dose. The side-effects observed in our infants were transient and no long-term complication was attributable to this drug.

Ductus Arteriosus, Patent↗
PubMed1983

Cefoxitin in newborn infants. A clinical and pharmacokinetic study.

Fifteen patients less than 2 months old with bacterial infections caused by pathogens known or presumed to be sensitive to cefoxitin were studied. Cefoxitin was administered as an i.v. bolus injection over 15 min, every 8 h for 6 to 12 days, to a total daily dosage of 90 mg/kg. In 14 patients cefoxitin therapy resulted in eradication of the pathogen and in recovery from clinical signs of infection. Only one patient did not respond to cefoxitin therapy. No adverse clinical or haematological effects definitely caused by cefoxitin were observed. Plasma and urine samples collected after the first dose were assayed for cefoxitin by HPLC. Pharmacokinetic data indicated larger apparent volume of distribution (0.5 1/kg), a smaller plasma clearance (0.27 1/h/kg) and a longer half-life (1.43 h) than in adults. The plasma half-life was inversely correlated (p less than 0.05) to the postnatal age of the patients. Cefoxitin may be safely used in infants with infections caused by susceptible pathogens.

Bacterial Infections↗
PubMedDate not supplied

New strategies in immunosuppression.

New immunosuppressive strategies that can prevent both acute and chronic rejection are being investigated to achieve graft tolerance and to minimize side effects and toxicity that may lead to graft loss. Drug pharmacokinetics and pharmacodynamics, as well as pharmacogenetics, all play a role in customizing treatment to the individual patient. To improve patient compliance, new drug formulations are on trial, such as the modified- release oral form of tacrolimus MR4 for once daily administration, which seems to be equivalent to bid administration in terms of steady-state exposure. Monoclonal/polyclonal antibodies are increasingly used in the induction phase in protocols where steroids are discontinued early. However, discontinuing steroids carries a high risk of acute rejection or organ failure in some subgroups of patients. The supposed benefit of steroid discontinuation may not be enjoyed by all patients. Minimizing anticalcineurin agents may prove to be similarly or even more advantageous. The use of new drugs and new combinations has greatly improved short-term transplant outcomes. The new goal is, therefore, to improve long-term results and particularly to prevent chronic rejection, thus increasing patient and organ survival.

Humans↗
PubMedDate not supplied

[Pharmacokinetics of ceftriaxone in the first three month of life].

The purpose of the study was to define more precisely ceftriaxone kinetic variations in neonates and infants during the first three months of life. Ceftriaxone pharmacokinetics were studied in 14 newborns and infants with gestational age ranging from 31 to 42 weeks and younger than three months of postnatal age. Ceftriaxone was administered as an intravenous bolus injection over 15 min at a dose of 50 mg/Kg every 24 hours, for a period of 7 to 28 days according to the bacterial diseases. 13 patients had normal renal function and one had a chronic renal insufficiency. Plasma and urine concentrations were measured by a specific HPLC assay. The mean plasma concentration was 180.7 +/- 19.9 ug/ml (mean +/- SD) 30 min after the beginning of the infusion. After 24 h the plasma value was 29.9 +/- 10.0 ug/ml. The mean elimination half-life (t1/2) was 19.9 h, the total clearance (CL) of the drug was 0.38 ml/min/Kg and the volume of distribution (Vd) was 0.32 l/Kg. About 52% of the administered dose was excreted unchanged in urine. In the patient with renal insufficiency we observed t1/2 = 38.9 h and CL = 0.10 ml/min/Kg. Only a slight accumulation of the drug (from 180.7 +/- 19.9 ug/ml to 223 +/- 15.5 ug/ml) was observed during multiple dosing. The volume of distribution and the plasma half-life were significantly correlated (negative correlation) to the postnatal age. There was no correlation between clearance and postnatal age. No side effects were observed in newborns and infants after administration of ceftriaxone.

Bacterial Infections↗
PubMedDate not supplied

Itraconazole can increase systemic exposure to busulfan in patients given bone marrow transplantation. GITMO (Gruppo Italiano Trapianto di Midollo Osseo).

Busulfan (BU) is an alkylating drug frequently used to prepare patients for bone marrow transplantation (BMT). Several studies have documented that there is important interpatient variability in BU disposition and systemic exposure, and that other drugs with a common metabolic pathway are capable of influencing BU clearance. We compared the BU pharmacokinetics and pharmacodynamics of 13 patients given BMT and receiving BU and itraconazole, with those of 26 matched controls who did not receive any anti-fungal agent, and with those of 13 matched patients treated with fluconazole as prophylaxis against fungal infections. The effect of itraconazole was best reflected in BU clearance since the BU dose was modified in some patients. BU clearance was decreased by an average of 20% in patients receiving itraconazole as compared to control patients and patients receiving fluconazole (p < 0.01). Mean BU clearance was 7.653 +/- 1.871 l/hr.m2 in the itraconazole patients, 10.103 +/- 2.007 l/hr.m2 in the fluconazole group and 9.373 +/- 1.702 l/hr.m2 in the control group. In this study itraconazole, but not fluconazole, markedly affected the pharmacokinetics of BU as an increase of BU plasma concentrations was observed. The nature of this interaction has not yet been fully characterized. Itraconazole and its analogues are inhibitors of both cytochrome P450 and lipoxygenase and since itraconazole can modulate BU pharmacokinetics, oxidative catabolism is probably a determinant of BU metabolism. This hypothesis should be tested in human metabolic studies.

Adolescent↗