PubMed Health⌕ Search

Biomedical subjects

Patrice Jaillon

Publications and source records attributed to Patrice Jaillon.

24 records · Page 2Linked to original sources
PubMed2002

Renal and vascular effects of S21402, a dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase, in healthy subjects with hypovolemia.

OBJECTIVE: To examine the mechanism of action of dual inhibitors of angiotensin-converting enzyme (ACE) and neutral endopeptidase, also called vasopeptidase inhibitors, we compared the effects of S21402 [(2S)-2-[(2S,3R)-2-thiomethyl-3-phenylbutanamido]propionic acid], which belongs to this pharmacologic class, with those of captopril, an ACE inhibitor, on blood pressure, endocrine parameters, and renal in healthy subjects with hypovolemia. METHODS: Ten subjects participated to this double-blind, 2-period, randomized, crossover study. Hypovolemia was induced in these subjects with a 7-day treatment of hydrochlorothiazide. They received a single oral dose of 50 mg captopril or 250 mg S21402 on the last day of diuretic treatment. Blood pressure was measured, and urine and blood samples were collected before and during a 12-hour period after drug administration. RESULTS: The plasma angiotensin II/angiotensin I ratio and aldosterone concentration decreased to the same degree with both drugs, 3 hours after dosing. Compared with captopril, S21402 increased levels of plasma atrial natriuretic peptide (P <.05) and urinary cyclic guanosine monophosphate (P <.001); these increases were the result of inhibition of neutral endopeptidase activity (P <.001). The increase in plasma renin concentration related to ACE inhibition was less marked (P <.001) after S21402 than after captopril. S21402, but not captopril, increased urinary sodium excretion (P <.05), without modifying blood pressure and creatinine clearance, whereas blood pressure transiently fell after captopril administration (P <.05). CONCLUSIONS: In healthy hypovolemic subjects, the vasopeptidase inhibitor S21402 exhibits a natriuretic effect and does not affect blood pressure or glomerular filtration rate. In these conditions, the acute endocrine, vascular, and renal effects of vasopeptidase inhibition differ from those of ACE inhibition.

Adult↗
PubMed2002

Simultaneous determination of the six HIV protease inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir) plus M8 nelfinavir metabolite and the nonnucleoside reverse transcription inhibitor efavirenz in human plasma by solid-phase extraction and column liquid chromatography.

A sensitive and selective liquid chromatographic assay has been developed for the determination of the six currently protease inhibitors approved by the U.S. Food & Drug Administration (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir) plus the M8 active metabolite of nelfinavir and the nonnucleoside reverse transcription inhibitor efavirenz in a single run. Pretreatment of 1-mL plasma sample spiked with internal standard was made by a solid-phase extraction procedure using a polymeric reversed-phase sorbent. Liquid chromatography was performed using a narrow-bore C18 reversed-phase column and gradient elution. Double ultraviolet detection at 265 nm (amprenavir) and at 210 nm (all other assayed drugs and internal standard) was used. Calibration curves were linear in the range 25 to 10,000 ng/mL, and the assay has been validated over the range 25 to 5,000 ng/mL. Average accuracies at four concentrations were in the range 92.4% to 103.0% and 94.4% to 103.0% for within-day and between-day, respectively, and the coefficients of variation were less than 8%. Mean absolute recoveries varied from 72.8% (ritonavir) to 93.7% (indinavir). No metabolite of the protease inhibitors was found to coelute with the drugs of interest or with the internal standard. At this time, among the tested drugs, especially all the currently licensed nucleosides and the other nonnucleoside reverse transcription inhibitor nevirapine that can be used in combination with the protease inhibitors, none was found to interfere with the assay.

Alkynes↗
PubMedDate not supplied

Public information about clinical trials and research.

Be it to restore the confused image of clinical research in relation to the lay public, or to develop new ways of accruing healthy volunteers or patients for clinical trials, there is a need to draft some guidance on how best to provide information on research. Although the French legal and regulatory armamentarium in this area is essentially liberal, there is currently little-justified reluctance among study sponsors to advertise publicly. A group of academic and pharmaceutical industry researchers, assembled for a workshop, together with regulators, journalists, representatives from ethics committees, social security, patient and health consumer groups and other French institutional bodies, has suggested the following series of recommendations: there is no need for additional legal or regulatory constraints; sponsors should be aware of and make use of direct public information on trials; a 'good practice charter' on public communication about clinical trials should be developed; all professionals should be involved in this communication platform; communication in the patient's immediate vicinity should be preferred (primary-care physician, local press); clinical databases and websites accessible to professionals, but also to patients and non-professionals, should be developed; genuine instruction on clinical trials for physicians and health professionals unfamiliar with such trials should be developed and disseminated; media groups should receive at least some training in the fundamentals of clinical research.

Clinical Trials as Topic↗
PubMedDate not supplied

Effects of malnutrition on cytochrome P450 1A2 activity in elderly patients.

Little is known of the influence of nutritional status on cytochrome P450 (CYP) 1A2 activity in elderly patients. Thirty elderly institutionalised patients with malnutrition (group A, aged 88 +/- 5 years) and 24 without (group B, aged 81 +/- 9 years) were included. Malnutrition was defined as weight loss of >10% over the previous 6 months and/or a body mass index (BMI) <21 kg/m2 and albuminaemia < or = 32 g/L. CYP1A2 activity was evaluated by the plasma paraxanthine/caffeine (PAX/CAF) metabolic ratio. The plasma PAX/CAF metabolic ratio was similar in both groups regardless of nutritional status (0.34 +/- 0.13 [A] versus 0.30 +/- 0.11 [B]; p = 0.11). The CYP1A2 metabolic ratio was not correlated to either BMI, serum albumin or renal clearance. CYPI A2 activity, as measured by the plasma PAX/CAF ratio, was not influenced by nutritional status in elderly patients.

Aged↗
PubMedDate not supplied

The respective roles of controlled clinical trials and cohort monitoring studies in the pre- and postmarketing assessment of drugs.

The respective roles of controlled clinical trials and observational studies (cohort or case-control studies) in evaluating the efficacy, safety and usefulness of a drug were analysed. A randomised, controlled, double-blind study is the best method of estimating the efficacy of a treatment. It provides the least biased and most robust estimate of the causal relationship. In certain situations and on the basis of certain criteria, observational studies can have a proof-of-efficacy value. Randomised, controlled, pre- and postmarketing authorisation (MA) clinical studies identify the rarer adverse effects and compare them with those resulting from the reference treatment. Before the MA, the pooled safety data from different controlled trials can provide an estimation of relatively frequent adverse events and subjects at risk. However, an observational study is the most appropriate method of evaluating the safety of a drug in the currently used conditions. By definition, a drug influences the health of a population if it directly or indirectly improves its health. A drug would have a major role in public health if it reduced mortality or morbidity related to a particular disease or if it improved the quality of life of patients with this disease. Prior to marketing a product, modelling is the approach of choice to quantify the expected effect. Pragmatic, postmarketing trials and observational studies are the reference methods used to define the population affected, the efficacy and safety of the drug in a real situation and its usefulness for public health. In conclusion, randomised clinical trials remain the reference approach for evaluating efficacy, while observational studies have a confirmatory value. Observational studies are the most appropriate way of evaluating safety in the currently used conditions, as the clinical trial has limited indications. In the interests of public health, modelling is the pre-marketing approach of choice, while pragmatic trials and observational studies are the postmarketing reference approaches.

Cohort Studies↗