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A Cipriano

Publications and source records attributed to A Cipriano.

15 recordsLinked to original sources
PubMed2001

Fosinopril-induced prolonged cholestatic jaundice and pruritus: first case report.

We report a case of fosinopril-induced prolonged cholestatic jaundice and pruritus in a 61-year-old man, with no previous hepatobiliary disease, who presented with asthenia, jaundice and itching 3 weeks after starting fosinopril therapy. Other drugs taken by the patient were not considered probable causes. The diagnostic evaluation showed no biliary obstruction and other possible causes of intra-hepatic cholestasis were excluded. Liver biopsy showed cholestasis without bile duct damage. The disease ran a severe course during the 2 months of hospitalization, with prolonged itching for 6 months, eventually controlled with oral naltrexone. Jaundice subsided after 4 months, with anicteric cholestasis persisting for more than 18 months. Similar occurrences have been reported with other inhibitors of angiotensin-converting enzyme (mostly captopril), but this is the first case of an important adverse reaction to fosinopril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Ticlopidine-induced prolonged cholestasis: a case report.

We report a case of ticlopidine-induced prolonged cholestasis in a 60-year-old man with no previous hepatobiliary disease who presented with sudden right upper abdominal pain, jaundice and pruritus three months after starting ticlopidine therapy. Other drugs taken by the patient were not considered probable causes. The diagnostic evaluation showed no biliary obstruction and other possible causes of intra-hepatic cholestasis were excluded. The liver biopsy showed a cholestatic hepatitis with bile duct damage. The disease ran a severe and protracted course, but symptoms and jaundice eventually subsided five months after drug withdrawal. More than a year later, relevant abnormalities of liver function tests consistent with anicteric cholestasis still persist, fulfilling criteria for a minor form of drug-induced prolonged cholestasis. This syndrome has been reported infrequently in relation to several drugs, mainly chlorpromazine, and only once with ticlopidine.

Cholestasis↗
PubMed1999

A model of internal control may improve the response time of an automatic arterial pressure controller.

A simplified model for the arterial pressure control system was implemented on a personal computer using Matlab Simulink. Model responses to variations of systemic vascular resistance were comparable to those predicted by physiology. Computer simulation suggested that including this model of the internal pressure control system within the design of an external controller would achieve better arterial pressure control and faster response than previous systems.

Blood Pressure↗
PubMed1998

Quantitative analytical methods for the determination of a new hypertension drug, CGS 25462, and its metabolites (CGS 25659 and CGS 24592) in human plasma by high-performance liquid chromatography.

Two simple and sensitive reversed-phase high-performance liquid chromatography (HPLC) methods were developed and validated for the quantitative determination of a novel hypertension drug CGS 25462 and its major metabolites CGS 24592 and CGS 25659 in human plasma. CGS 25462 and CGS 25798 (internal standard) were purified by one-step liquid-liquid extraction with methylene chloride. The metabolites were analyzed on HPLC after plasma protein precipitation with 10% trichloroacetic acid (TCA). Separations were achieved on a Zorbax RX C18 column. All compounds were detected by using a fluorescence detector. The excitation wavelength was 254 nm, and emission was monitored at 325+/-12.5 nm. Assessment of recovery and reproducibility indicated good accuracy and precision. Over the validation concentration range of 10 to 1000 ng/ml for CGS 25462 and 25 to 5000 ng/ml for both metabolites, overall mean relative recoveries were 96% for CGS 25462, 101% for CGS 25659 and 107% for CGS 24592, and the coefficients of variation were 4.6 to 13% for CGS 25462, 9.5 to 13% for CGS 25659 and 7.7 to 15% for CGS 24592. The limits of quantification (LOQs) were 10 ng/ml for CGS 25462 and 25 ng/ml for CGS 24592 and CGS 25659, which were of sufficient sensitivity to measure the concentrations of CGS 25462, CGS 25659 and CGS 24592 in plasma samples from normal volunteers following a single 800 mg oral dose.

Administration, Oral↗
PubMed1998

Estimation of ventricular volume and elastance from the arterial pressure waveform.

We propose that it is possible to estimate cardiovascular parameters from the arterial pressure waveform, including ventricular maximal elastance and end-diastolic volume, if cardiac output is also known. We tested this hypothesis by means of a parameter estimation algorithm applied to simulated arterial pressure signals. The program first estimated three coefficients representing products of passive parameters from the diastolic part of the simulated arterial pressure waveform. Second, it estimated three parameter products pertaining to the ventricular function from the systolic part of the waveform. Third, mean blood flow was entered, enabling the program to compute individual parameters. This program was tested on 200 computer-generated arterial pressure signals, obtained by simulating the model with random but bounded parameters. Correlation between estimated parameters with those actually used in the simulations was excellent. Even though the value of this computer simulation is limited to the simplified model used and requires experimental validation, it demonstrates that the technique is theoretically feasible.

Blood Flow Velocity↗
PubMed1998

Estimation of cardiac function from computer analysis of the arterial pressure waveform.

This paper presents a method for estimating parameters of a cardiovascular model, including the left-ventricular function, using the sequential quadratic programming (SQP) and the least minimum square (LMS) algorithms. In a first stage, a radial arterial-pressure waveform with corresponding cardiac output are used to automatically seek the set of parameters of the diastolic model. Computer simulation of the model using these parameters generate a pressure waveform and a cardiac output very close to those used for the estimation. In a second stage, the estimated arterial load parameters are used to select the best left-ventricular model function, from four different possibilities, and to estimate its optimum parameter values. The method has been tested numerically and applied to real cases, using data obtained from cardiovascular patients. It has also been subjected to preliminary validation using data obtained from laboratory dogs, in which cardiovascular function was artificially altered.

Algorithms↗
PubMed1996

Explaining variable absorption of a hypolipidemic agent (CGP 43371) in healthy subjects by gamma scintigraphy and pharmacokinetics.

The gastrointestinal absorption of a hypolipidemic agent (CGP 43371) was investigated using an external scintigraphy technique in six healthy men. After an overnight fast, subjects received a single 800-mg oral dose of CGP 43371 (4 capsules of 200 mg each) and one capsule of radioactive samarium-153 oxide (100-130 microCi) as a nonabsorbable marker of gastrointestinal transit and fecal recovery for CGP 43371. In vivo gastrointestinal transit of samarium-153 was monitored via gamma scintigraphy for 48 hours after administration to coincide with blood sampling. Samarium-153 content in whole fecal samples was determined by external gamma scintigraphy, and CGP 43371 content in both fecal and plasma samples was determined using high-performance liquid chromatography (HPLC). The results of fecal analysis indicated that transit of the two compounds in the gastrointestinal tract were similar, and bioavailability of CGP 43371 was calculated to be 9% based on the difference between the cumulative amounts of the nonabsorbable radioactive marker and CGP 43371 found in the feces. The onset of drug absorption occurred 4 hours after administration when radioactive samarium-153 was in the distal small bowel, and peak plasma drug level occurred 6 hours after administration, which corresponded with the arrival of samarium-153 in the terminal ileum and ileal/cecal junction. This observation supported the concept that primary absorption of this compound was in the distal to terminal portion of the ileum. Although the onset of drug absorption was delayed, it was curious that the rate of gastric emptying also affected the extent of absorption. A positive correlation (r = 0.91) between area under the drug curve (AUC) and area under the transit curve (AUTC) of the gastric emptying showed that longer gastric residence improved oral absorption of CGP 43371.

Adult↗
PubMed1995

Comparative pharmacokinetics and bioavailability of nitroglycerin and its metabolites from Transderm-Nitro, Nitrodisc, and Nitro-Dur II systems using a stable-isotope technique.

The pharmacokinetics and bioavailability of nitroglycerin (GTN) and its metabolites, 1,2-glyceryl dinitrate (1,2-GDN) and 1,3-glyceryl dinitrate (1,3-GDN), were compared after a single 14-hour application of Transderm-Nitro (Ciba-Geigy, Summit, NJ), Nitrodisc (GD Searle, Chicago, IL), and Nitro-Dur II (Key Pharmaceuticals, Kenilworth, NJ) systems to 18 healthy male subjects on 3 separate occasions. A 14-hour intravenous infusion of 15N-labeled GTN was given simultaneously to correct for changes in systemic clearance during the application of each system. Plasma concentrations of 15N-labeled GTN, unlabeled GTN, and their corresponding dinitrate metabolites were measured using a gas chromatography/mass spectrometry method. Results showed that the plasma concentration profiles of nitroglycerin and its metabolites for the three systems were similar during and after system removal. Mean (SD) total amounts (AUCp x CLiv) of GTN transdermally available after adjustment for 15N-labeled GTN clearance were 5.3 (2.1), 5.3 (2.0), and 5.4 (2.6) mg for Transderm-Nitro, Nitrodisc, and Nitro-Dur II, respectively. Mean (SD) AUC values for 1,2-GDN were 44.6 (15.8), 44.3 (16.1), and 42.8 (19.3) ng.h/mL for the 3 systems. Corresponding AUC values for 1,3-GDN were 9.3 (2.9), 9.7 (2.9), and 8.7 (3.0) ng.h/mL. Statistical analysis of the log-transformed data based on 90% conventional confidence interval showed that all 3 systems delivered equivalent amounts of nitroglycerin into the systemic circulation. The AUC ratios for 1,3-GDN to GTN, but not 1,2-GDN to GTN, were statistically different for the intravenous and transdermal routes during all 3 system applications, indicating that the formation and metabolism of 1,3-GDN was dependent on route of administration.

Administration, Cutaneous↗
PubMed1994

Effect of food on the relative bioavailability of a hypolipidemic agent (CGP 43371) in healthy subjects.

The relative bioavailability of a capsule formulation and the effects of food on the pharmacokinetics of a hypolipidemic agent (CGP 43371) in 12 healthy subjects were examined. Each subject randomly received a single dose of 800 mg of CGP 43371, either as a dispersion formulation under fasting conditions or as a capsule formulation under fasting and fed conditions in a three-way crossover design with a washout period of 2 weeks between each treatment. Serial blood samples were collected at frequent intervals up to 96 h after each treatment. The concentrations of CGP 43371 in plasma were determined by a normal-phase HPLC method. Similar mean pharmacokinetic data (peak plasma drug concentration, 0.16 versus 0.18 micrograms/mL; area under the plasma drug concentration-time curve from time zero to infinity, 4.56 versus 4.22 micrograms.h/mL; time to the peak plasma drug concentration, 10.3 versus 10.2 h; lag time, 3.7 versus 3.8 h; and terminal elimination half-life, 17.8 versus 15.0 h) for the dispersion and capsule formulations under fasting conditions indicated that both formulations were bioequivalent with respect to the rate and extent of absorption. In contrast, the mean peak plasma drug concentration (2.01 micrograms/mL) and area under the curve from time zero to infinity (57.35 micrograms.h/mL) for the capsule formulation with food were enhanced approximately 11- and 14-fold, respectively, when compared with that without food. The corresponding mean lag time (2.1 h) was decreased approximately 50%. These differences in pharmacokinetic parameters were statistically significant, on the basis of an analysis of variance.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticholesteremic Agents↗
PubMed1994

Pharmacokinetic interaction study between benazepril and amlodipine in healthy subjects.

Pharmacokinetic interaction between benazepril (ACE inhibitor) and amlodipine (calcium channel blocker) was studied in 12 healthy subjects. Single doses of benazepril hydrochloride (10-mg tablet) and amlodipine besylate (tablet equivalent to 5 mg amlodipine) were administered alone or in combination according to a three-way, Latin-Square, randomized cross-over design. Serial blood samples were collected following each administration for the determination of benazepril and its active metabolite benazeprilat and amlodipine. The mean values of AUC (0-4 h), Cmax and Tmax for benazepril given as combination versus given alone were 161 vs 140 ng.h.ml-1, 168 vs 149 ng.ml-1, and 0.5 vs 0.6 h. The mean values of AUC (0-24 h), Cmax and Tmax for benazeprilat after benazepril given as combination versus given alone were 1470 vs 1410 ng.h.ml-1, 292 vs 257 ng.ml-1, and 1.7 vs 1.5 h. The mean values of AUC (0-144 h), Cmax and Tmax for amlodipine given as combination versus given alone were 118 vs 114 ng.h.ml-1, 2.5 vs 2.3 ng.ml-1, and 8.3 vs 9.0 h. The differences in these pharmacokinetic parameters between the combination and monotherapy treatments were not statistically significant based on ANOVA. The results of this study indicate that no pharmacokinetic interaction existed between the two drugs.

Adult↗
PubMed1994

[Effect of chronic blockade of the opiodergic receptor on insulin resistance in a hyperandrogenic woman].

We report a woman with insulin resistance associated with hyperandrogenism and acanthosis nigricans (HAIR-AN syndrome) treated during 30 days with the prolonged action opioid antagonist Naltrexone. During its administration, decreases in basal blood glucose and serum insulin, insulin and glucose response to a glucose load and plasma testosterone were observed. These findings suggest that opioid activity could play a critical role in the physiopathology of hyperinsulinemia in hyperandrogenic women.

Acanthosis Nigricans↗