Pharmacokinetic and pharmacodynamic variability of fluindione in octogenarians.

In the PREPA observational study, we investigated the factors influencing pharmacokinetic and pharmacodynamic variability in the responses to fluindione, an oral anticoagulant drug, in a general population of octogenarian inpatients.Measurements of fluindione concentrations and international normalized ratio (INR ) were obtained for 131 inpatients in whom fluindione treatment was initiated. Treatment was adjusted according to routine clinical practice. The data were analyzed using nonlinear mixed-effects modeling, and the parameters were estimated using MONOLI X 3.2. The pharmacokinetics (PK) of fluindione was monocompartmental, whereas the evolution of INR was modeled in accordance with a turnover model (inhibition of vitamin K recycling). Interindividual variability (II V) was very large. Clearance decreased with age and with prior administration of cordarone. Patients who had undergone surgery before the study had lower IC50 values, leading to an increased sensitivity to fluindione. Pharmacokinetic exposure is substantially increased in elderly patients, warranting a lower dose of fluindione.

Fatal acute poisoning by bentazon.

A case of fatal suicidal bentazon poisoning is presented along with a description of the different analytical methods involved. A 56-year-old farmer was examined by the family doctor 1 h after voluntarily ingesting 500 mL of FIGHTER (bentazon, 480 g/L water). He presented a Glasgow score of 15, polypnea, diarrhea, and vomiting. During transport by ambulance to the hospital, he tossed, sweated, and suddenly presented breathing difficulty followed by heart failure. Tracheal intubation was impossible (H1.5) despite use of different diameter cannulas because of extreme general muscle rigidity. All attempts at resuscitation failed, and the patient died within 2 h postingestion. Blood and urine samples were taken just before death. General basic and neutral drug screening by high-performance liquid chromatography-diode-array detection and gas chromatography-nitrogen-phosphorus detection showed no strychnine or other drugs or toxics except for citalopram (< 0.1 mg/L) and bentazon, but this weak acidic molecule (pKa3.3) was badly extracted in alkaline conditions. Plasma and urine levels, measured after acidic extraction, protein precipitation, or simple dilution, were 1500 and 1000 mg/L, respectively. Bentazon (M.W. 240) was confirmed by its basic mass spectrum (ESI-, m/z 239, 197, 175, 132) or by that of methylated derivative (El+, m/z 254, 212, 175). An hydroxylated metabolite (ESI-, m/z 255, 213, 191, 148; El+, m/z 284, 242, 163) and the N1-glucuronide conjugate of bentazon (ESI-, m/z 415, 239) were also detected in urine. (Quantitation ions are underlined.) This first case of bentazon poisoning with available analytical data revealed the high toxicity of this compound after large dose ingestion with early and heavy symptoms such as muscle rigidity probably related to muscular toxicity. Comparison with another nonfatal case and with toxicological data on animals is discussed.

[Retrospective study of adverse drug reactions in the elderly: experience of regional center for pharmacovigilance]. / Etude rétrospective de la iatrogénie médicamenteuse chez le sujet âgé: expérience d'un centre régional de pharmacovigilance.

Cases of adverse drug reactions which occurred in the elderly, and were notified to the Regional Centre of Pharmacovigilance of Angers between 1995 and 1998, were analysed in two subgroups: from 75- to 84-years-old and older than 84 years. Among the 263 cases recorded in the elderly, there was no significant difference between the 75- to 84-year-old patients (180 cases) and the patients older than 84 years (83 cases) concerning past medical history, severity of effects or medication. Side-effects in patients over 74 were mainly cutaneous, haematological and neuropsychiatric, involving in decreasing order of frequency cardiovascular, neuropsychiatric, antibiotic, analgesic and anti-inflammatory drugs. In comparison with patients under 75, adverse drug reactions are more frequent and more serious, notably overdose and drug interactions, in elderly people. The occurrence of some avoidable side-effects justifies the strengthening of information about therapeutic safety in the elderly.

Polypoid formations at the anal margin in infants less than two years old.

Polypoid formations in the anal canal and at the anal margin are sometimes observed in the newborn and in infants less than 2 years old. Unlike hamartomatous polyps, which are commonly reported in infantile proctology, these growths are rare in early childhood. Only by performing a pathological anatomy examination is it possible to determine the nature of the numerous affections encountered to assess prognosis and to decide on suitable therapeutic management.