Trends in antihypertensive drug use among orally treated diabetic patients, in France between 1981 and 1992. Impact of guidelines and new drugs.

OBJECTIVE: To compare antihypertensive drug use between diabetics and non-diabetics and to analyse the change between the two last decennial national surveys on health and medical care in France, in 1981 and 1992. MATERIAL AND METHODS: These surveys included respectively 12,725 and 13,887 adults over 25 years. Use of all antihypertensive drugs marketed in France was compared between orally treated diabetics and non-diabetics who were non-insulin and non-oral anti-diabetic treated population. RESULTS: In 1981, while diuretics were the first treatment in both populations (53% in diabetics vs 60% in non-diabetics, non significant), central inhibitors (31 vs 16% respectively, p<0.001) were the second agent among diabetic patients instead of beta blockers in non-diabetic patients (13 vs 22% respectively, p<0.05). In 1992, beta blockers were also less used in diabetics (21 versus 33%, p=0.001). In contrast, ACE inhibitors were more used (43 versus 35%, p=0.06). In both surveys and populations, other classes (reserpin, vasodilator and alpha blockers) had minor place in the strategy. The frequency of combinations of antihypertensive drugs was similar in both surveys and populations. The preferred combination treatment was in both populations reserpin with diuretics in 1981 (7 vs 9%, non significant) and ACE inhibitors with diuretics in 1992 (18 vs 18%). CONCLUSION: Independently of guidelines, our data suggest that the strategy of hypertension treatment has changed last years and that prescriptions were more targeted for diabetic patients.

[Totally reimbursed care for type 2 diabetes in 1994: characteristics and follow-up]. / Le diabète de type II pris en charge à 100 % en 1994 : caractéristiques et suivi.

Non-insulin-dependent diabetes mellitus (NIDDM) is an important health issue in France. According to projections from current data, the problem should increase over the upcoming years. The aim of this study was to determine the characteristics of patients with NIDDM who are enrolled on the list of 30 long term diseases (ALD30) and examine their follow-up and disease-related complications. This study was performed with the data base established by the French National Health Insurance for Salaried Workers (CMANTS) in 1994. Diagnosis and medical information were coded by official physicians, who either examined the patients or consulted their primary care physician (69% of the cases), or relied on available medical records. Eight thousand two hundred forty-seven patients (sex ration=0.95) with NIDDM enrolled on the long term disease list were included. Mean age was 65.1+/- 0.13 years (m+/- SEM). More than one blood glucose level per year was available for 89% of the patients and an HA1c assay in only 34%. In addition, for patient follow-up at least once a year, 80%, 47%, and 42% of the patients had a serum creatinine assay, a funus examination, or an electorcariogram respectively. Irrespective of the criteria retained (fasting glucose=1.26 g/l; fasting glucose=1.40 g/l) there was a high percentage of patients whose level was well above the limit (75% and 63% respectively). For HbA1c, only a quarter of the patients had values lower than the limits defined by the ANAES and AFFSAPS guidelines. The percentage of diabetic patients without complications was 41% (hypertension excluded). The most frequently observed complications isolated peripheral vascular conditions (31%). These results were obtained from a database created in 1994, before guidelines on type 2 diabetes were officially published. They can serve as a reference to follow medical practices.

[Pharmacoepidemiology of diabetes: assessment of good use of oral antidiabetic drugs]. / Pharmacoépidémiologie du diabète : évaluation du bon usage des antidiabétiques oraux.

Diabetes' treatment is specific; therefore diabetic patients can be identified by the prescription of antidiabetic drugs. This pathology is characterized by chronicity and occurrence of complications which need additional medications. All the drugs have official use guidelines due to drug interactions and/or physiological status of the patients. To evaluate how these guidelines are followed in general practice, we used a data base from the French Health care System. Two thousand eight hundred and ninety eight (2 898) prescriptions on which, at least, one oral antidiabetic drug was noticed, were analysed. The number of drugs on each prescription was between 1 and 18 (mean (5,6 +/- 2,9)). Considering the drugs which need precautions of use in association with sulfonylureas, coprescription occurred with B-bloquants and non steroid anti-inflammatory drugs in 18 and 17 % of the cases respectively. The drugs which need precautions of use in association with biguanides were diuretics, oestrogens and/or progestatives and steroids, coprescribed in 28, 1, 1 % of the cases respectively. Percentages of coprescriptions which need precautions of use were quite high. The relevance of detected coprescriptions. and the compatibility between recommendations for "good prescription" and "real prescription practice" should be taken into account considering diabetic patients' characteristics.

Analysis of mortality in French diabetic patients from death certificates: a comparative study.

This study was implemented in France to determine the causes of death in diabetic patients, whether diabetes was mentioned or not on the death certificate, and to assess the underestimation of the prevalence of diabetes at death. Two stratified random samples of death certificates were selected in the national mortality data base. The first included certificates mentioning diabetes as a cause of death (cases). The second, included certificates with no mention of diabetes (controls). For each certificate, a record form was sent to the certifying physician to ascertain diabetes in the first group and to trace unrecorded diabetes in the second group. In case of diabetes, the characteristics of the patient and his disease were collected (age at onset, treatment, complications ...). We obtained complete data for 325 cases and 959 controls. Among cases, 1% of the subjects were not confirmed as diabetic, while almost 10% of the controls were identified as having diabetes. The corresponding ratio of the corrected prevalence at death to that provided by the French statistics was estimated to 4.0 in men and 3.1 in women. Particular features are that 2% of the total diabetic decedents died from acute metabolic complications (diabetic or hyperosmolar coma, acidoketosis, or acute hypoglycemia), and that 33% of the unreported diabetic decedents under 45 died from trauma or poisoning. These results show that in France, the death rates published in the statistics for diabetes dramatically underestimate the impact of diabetes. A high risk of death is linked to this disease, particularly in people aged under 45, a problem that health deciders should address.

[Epidemiology, management and costs of type 2 diabetes in France in 1998]. / Epidémiologie, prise en charge et coût du diabète de type 2 en France en 1998.

Almost 10 years after the Saint Vincent declaration, a large effort was undertaken in France to improve medical care of type 2 diabetes and to limit the dreadful complications of this pathology. As expert recommendations grow in number, it appears necessary to update knowledge on the epidemiological, medical care, and cost aspects of this illness in France. In this aim, a systematic review of the medical and economic literature on type 2 diabetes was performed. Prevalence of type 2 diabetes probably reaches 2.2% in the general population, which represents 1.3 million people in France. Among these people, almost 60% are overweighted, 50% suffer high blood pressure and 30% have a treated dyslipaemia. Coronary pathologies concern 20% to 30% of type 2 diabetes patients, neuropathies 10% to 30% and ocular problems 10% to 35%. Medical care consumption of type 2 diabetes patients probably represents almost 20,000 FF per patient and per year, i.e., twice the average medical care consumption in the French population. Yet, these estimates should be considered with caution since a lot of uncertainty remains on the epidemiological, medical care, and cost aspects of type 2 diabetes in France. As diabetes has become a national public health priority, it is important to initiate new studies to have precise indicators in these different fields.

[Pharmacoepidemiology of diabetes: contribution of a survey of health insurance cases]. / Pharmacoépidémiologie du diabète: apports d'une enquête des Caisses d'Assurance Maladie.

To determine the pattern of treatment of diabetes and its complications, data from a specific study performed by the French healthcare system were used. Between the 10th and 15th of May 1993, all the prescriptions for which a reimbursement was asked were registered with the age and sex of the subject for whom the prescription was written. Patients with a prescription of antidiabetic (AD) drugs were classified as diabetic. Among the 125,883 prescriptions at least one antidiabetic drug is present on 3339 (2.7%). The mean number of AD drugs prescribed is 1.3 and varies from 1 to 4. Eighty five per cent of the patients are treated with oral anti diabetic drugs alone (OAD) and 15% with insulin, alone (89%) or in association with OAD (11%). The total number of drugs (antidiabetic drugs included) prescribed for one patient varied from 1 to 18 (mean: 5.7) and is higher in women than in men. Drugs which are indicated in cardiovascular diseases (lipids lowering, blood pressure lowering drugs) are more frequent on "diabetic" prescriptions than on non diabetic ones. Most (66%) of the prescriptions are written on special forms (100% reimbursement). These forms are more often used for insulin treated patients (87%) than for non insulin treated patients (62%). Most (91%) of the prescriptions are written by a general practitioner. Taking into account the antidiabetic drugs specificity and the data base used, these results can be extrapolated to the all french diabetic population.

Estimation of the prevalence of orally treated diabetes in France using a pharmacoepidemiologic approach: comparison between 1981 and 1992.

PURPOSE: Non-insulin-dependent diabetes may become a public health problem in the next decade, given the increasing life expectancy of populations and because the baby-boom generation will reach the age at risk. Moreover a modification of the diagnostic criteria may increase the number of diabetic patients. We studied the evolution of diabetes prevalence. METHODS: A non-specific household survey, performed every 10 years was used. Patients who bought an oral antidiabetic drug during these studies were classified as diabetics. RESULTS: In 1980-81 and 1991-92 the crude diabetes prevalences were not significantly different even if there was a trend to increase (1.27% and 1.41%, respectively). When the 1980-81 prevalence was standardized to the age distribution of the 1991-92 sample, the trend disappeared (prevalence 1980-81:1.35%). CONCLUSION: There was no increase in an individual's risk of diabetes. However the crude prevalence tended to increase because of the changing age structure of the population. On-going studies are needed to follow the prevalence of diabetes during the next decade.

Trends in aspirin, paracetamol and non-steroidal anti-inflammatory drug use in children between 1981 and 1992 in France.

OBJECTIVE: Antipyretic/analgesic drugs (AADs) are among the most commonly used drugs in children. Their efficacy and adverse effects have often been debated and new AADs have been introduced over the past few years. The aim of this study was to assess the characteristics of the use of AADs in children in France, and their trends. METHODS: Two surveys on household health care consumption were undertaken in France, in 1981 and in 1992. They included 5060 and 4841 children, respectively. The AADs studied were aspirin, paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs). RESULTS: The proportion of children exposed to AADs increased significantly between 1981 and 1992 (+28% in 11 years). Among them, the percentage of subjects treated with aspirin decreased (-27%). In contrast, the percentage increased for paracetamol (+ 19%) and for NSAIDs (+179%). Aspirin was the AAD most used in 1981 (57.4%) and it was replaced by paracetamol in 1992 (71.6%). Nasopharyngitis was the main reason for AAD prescription under the age of 11 years; for older children it was influenza-like syndrome, irrespective of the study year. A change in AAD choice occurred in nasopharyngitis, acute bronchitis and influenza-like syndrome irrespective of the age group, and in otitis/sinusitis between 4 and 10 years. In all these cases aspirin prescription decreased, in contrast with paracetamol and NSAIDs. Self-medication of AAD was uncommon (8.3% for aspirin and 10.3% for paracetamol in 1992) and decreased (-29% and -33%). It was used principally for nasopharyngitis, influenza-like syndrome and pain. CONCLUSION: The consumption of AADs in children is high and is increasing. Paracetamol and NSAIDs tend to replace aspirin prescription in children and physicians have played the main role in this change.

[Retrospective survey of fluoroquinolone use in children]. / Enquête rétrospective sur l'utilisation des fluoroquinolones en pédiatrie.

BACKGROUND: Fluoroquinolones (FQ) are contraindicated in children because of the risk of cartilage damage. POPULATION AND METHODS: A retrospective survey concerning the use of FQ in children during the first 6 months of 1993 was organized in 1994. One hundred and sixty-seven Heads of pediatric departments were questioned. RESULTS: One hundred and fifty (90%) of those surveyed responded: 62 (41.3%) were FQ prescribers, 83 (55.3%) were non prescribers and five (3.4%) were not able to answer. Among the 62 prescribers of FQ, 17 departments (27%) were not able to indicate the number of prescriptions and 45 departments (73%) reported one to 75 prescriptions during the study period. Twenty-one departments out of the 45 were not able to identify the children treated with FQ. We obtained a group of 104 children aged 9.0 +/- 5.0 years (mean +/- standard deviation [SD]), treated with 165 courses of FQ during 20 +/- 45 days (1-535 days) with concomitant treatments for 132/165 courses (80%). Fifty children (48%) were suffering from cystic fibrosis, 37 children (36%) were not, and, in 17, the diagnosis was not determined (16%). The FQ treatment administered either orally (73%) or intravenously (26%) was ciprofloxacin in 69% of the courses with a 25.1 +/- 7.0 mg/kg/day oral dose (mean +/- SD dose), and a 23.5 +/- 11.4 mg/kg/day intravenous dose, pefloxacin in 23 courses/165 (14%) with a 17.2 +/- 3.8 mg/kg/day dose, ofloxacin in 15 courses/165 (9%) with a 21.0 +/- 11.9 mg/kg/day dose, norfloxacin in 13 courses/165 (8%) with a 25.6 +/- 7.5 mg/kg/day dose. Twenty-one adverse events were reported in 17 children (16%) (11 of them with cystic fibrosis). These were cutaneous events (photosensitivity, cutaneous eruption) in eight courses, rheumatologic events (arthralgia, arthritis) in seven courses and gastrointestinal events (nausea, vomiting, diarrhea) in three courses. CONCLUSION: This survey shows that FQ are prescribed in children although their use is not approved in this age group and that numerous side effects have been recorded. The absence of exhaustive information (due to the retrospective nature of the survey) and the difficulties in interpreting the side effects for which validity and causal assessment have not been worked out according to a standardized method and in the absence of a control group stress the need for a prospective study.

Low prevalence of long-term complications in non-insulin-dependent diabetes mellitus in France: a multicenter study. CODIAB-INSERM-ZENECA Pharma Study Group.

The aim of this study was to assess the prevalence of long-term complications in a large sample of French NIDDM patients. Therefore, 427 NIDDM patients 35-74 years old were recruited in ten centers. Standardized clinical criteria and central reading for retinal and electrocardiographic changes were used to assess the presence of complications. The prevalence rates of complications were 29.7% and 3.3% for background and proliferative retinopathy; 21.8%, 6.1%, and 2.8% for microalbuminuria, proteinuria, and renal insufficiency; 19.9 and 11.7% for asymptomatic and symptomatic pheripheral neuropathy; 8.2% for orthostatic hypotension; 10.1% and 8.4% for angina pectoris and myocardial infarction; and 13.1% and 6.3% for mild and moderate to severe peripheral vascular disease, respectively. In conclusion, prevalence rates in this study were lower than in most studies from other countries.

Isoniazid dose adjustment in a pediatric population.

This retrospective analysis was designed to evaluate the inactivation index (I3) method used to adjust the isoniazid dose during long-term administration in a pediatric population. Before starting on antituberculosis therapy, sixty-one children received one 10 mg.kg-1 isoniazid test-dose (D). The isoniazid and acetyl isoniazid concentrations were measured by high-performance liquid chromatography on a plasma sample collected 3 hours (C3h) after administration. The patients were separated into slow and fast acetylator groups according to the metabolic ratio. The dose adjustment method using the I3 is based on the assumption that there is a linear correlation between C3h and D [C3h = (I3 x D) - 0.6] in which the slope is I3 and the Y intercept is equal to -0.6 mg.l-1. I3 was determined from a single plasma concentration determination and used to calculate the dose recommended to obtain a desired C3h equal to 1.5 micrograms.ml-1: recommended dose (mg.kg-1) = (1.5 + 0.6)/I3.I3 was significantly higher in the slow acetylator group (0.55 +/- 0.16) than in the fast one (0.26 +/- 0.13), which leads us to recommend a significantly lower dose in the slow acetylator group (4.2 +/- 1.5 mg.kg-1) than in the fast one (10.3 +/- 4.6 mg.kg-1). The data obtained in a subgroup of 21 patients who had at least three consecutive determinations of C3h after different dosages allowed us to verify that there was a linear correlation between C3h and the dose. The mean slope of the correlation lines in that subgroup was 0.61 +/- 0.25 and the 95% confidence interval of the estimated Y-intercept include the theoretical value of -0.60, which shows that our data are consistent with those previously reported in adults. The percentage of patients with a C3h plasma concentration within the expected range (1.5 +/- 0.5 micrograms.ml-1) was significantly higher (69%) in those whose dose was derived from the calculation than in the others (25%). Within each acetylator group, the range of the recommended dose varied widely, and these results emphasize the usefulness of individual dose adjustment based on the inactivation index method.

Inappropriateness and variability of antibiotic prescription among French office-based physicians.

OBJECTIVE: To describe oral antibiotic prescription in the community. DESIGN: Audit of anti-infective prescribing in office-based medical practice. SETTING: Center of France, in the Loiret, a 600,000 inhabitant administrative division. MAIN OUTCOME MEASURES: Clinical hypothesis and antimicrobial drugs used as well as daily doses and durations of treatment. RESULTS: Respiratory tract infections with a presumed viral etiology accounted for 36% of prescriptions. In children, a high percentage of antibiotic prescriptions were underdosed as compared to clinical recommendations, particularly in acute otitis media. The variability of the daily dose was high, with coefficients of variation over 40% in acute otitis media or acute tracheobronchitis. Whatever the clinical hypothesis, the duration of treatment was close to 8 days. In acute otitis media, the coefficient of variation was 14%, the lowest for all diagnoses. CONCLUSION: Our investigation identified two main areas for improving antimicrobial drug prescribing: (1) reduction of useless prescriptions in respiratory tract infections with a presumed viral etiology, and (2) increasing the prescribed daily dose of antimicrobials to the recommended levels.

Trends in antimicrobial drug use in the community--France, 1981-1992.

Trends in the use of antimicrobials in France between 1980-1981 and 1991-1992 were analyzed. Data were obtained from surveys of health and ambulatory care, which were based on national probability samples. In a 3-month period in 1980, 17% of the population of France was treated with an antibiotic, compared with 25% in 1991 (P < .001). The frequency of respiratory tract infections with a presumed viral etiology that were diagnosed and treated with antibiotics increased by 86% for adults and 115% for children in the 11-year period. The proper use of cephalosporins must be encouraged, and vigilance is required in view of the increased improper use of fluoroquinolones, mainly for respiratory tract infections with a presumed viral etiology.

Low dosage and long treatment duration of beta-lactam: risk factors for carriage of penicillin-resistant Streptococcus pneumoniae.

CONTEXT: The spread of drug-resistant Streptococcus pneumoniae in the community is a public health problem in developed and developing nations, but whether antibiotic use is responsible for the increase in drug resistance is not known. OBJECTIVE: To analyze the relationship between penicillin-resistant S pneumoniae (PRSp) pharyngeal carriage and characteristics of beta-lactam use. DESIGN: Observational study of children attending 20 randomly sampled schools. SETTING: The Loiret, in the center of France. PARTICIPANTS: A total of 941 children, 3 to 6 years old. MAIN OUTCOME MEASURE(S): Pharyngeal carriage of S pneumoniae, antibiotic use, and medical events during the preceding 30 days. Pneumococcal penicillin G sodium minimal inhibitory concentrations and serotyping were performed. RESULTS: Medical illnesses and the use of antibiotics were not associated with PRSp carriage. However, oral beta-lactam use was associated with an increased risk of PRSp carriage (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.1-8.3; P=.03). Children treated by low daily doses of an oral beta-lactam (defined as lower than clinical recommendations) had an increased risk of PRSp carriage, as compared with children who did not (OR, 5.9; 95% CI, 2.1-16.7; P=.002). A treatment of long duration (>5 days) with a beta-lactam was associated with an increased risk of PRSp carriage (OR, 3.5; 95% CI, 1.3-9.8; P=.02). CONCLUSIONS: Our results suggest that a low daily dose and a long duration of treatment with an oral beta-lactam contribute to the selective pressure in promoting pharyngeal carriage of PRSp.

Equivalent antipyretic activity of ibuprofen and paracetamol in febrile children.

The antipyretic activity of ibuprofen in the Sparklets form was compared, in an equivalence study, with that of paracetamol in the same formulation. The study was conducted as a double-blind multicenter trial, with random allocation of the treatments. One hundred sixteen children of both sexes, aged 4.1 +/- 2.6 years, with a fever related to an infectious disease and a mean temperature of 39 degrees +/- 0.5 degrees C at the time of inclusion, were treated with single doses of either 10.3 +/- 1.9 mg/kg of ibuprofen or 9.8 +/- 1.9 mg/kg of paracetamol. The subjects' rectal temperature was regularly monitored for 6 hours. The statistical analysis of the results confirmed that ibuprofen and paracetamol are equivalent with respect to the following criteria (1) time elapsed between dosing and the lowest temperature: 3.61 +/- 1.34 hours for ibuprofen and 3.65 +/- 1.47 hours for paracetamol (95% confidence interval [CI] of the difference: -0.48; +0.56); (2) extent of the temperature decrease: 1.65 degrees C +/- 0.80 degrees C for ibuprofen and 1.50 degrees C +/- 0.61 degrees C for paracetamol, (95% CI of the difference: -0.41; +0.11); (3) rate of temperature decrease: 0.52 +/- 0.32 degrees C/hr for ibuprofen and 0.51 degrees C +/- 0.38 degrees C/hr for paracetamol (95% CI of the difference: -0.45; +0.55); (4) duration of temperature below 38.5 degrees C: 3.79 +/- 1.33 hours for ibuprofen and 3.84 +/- 1.22 hours for paracetamol (95% CI of the difference: -0.14; +0.12).

Metoclopramide plasma concentration in neonates.

During the course of a multiple-dose metoclopramide (M) oral treatment, M plasma concentrations were measured just before (Cmin) and 1 hour after the administration (C1h) at steady-state in 5 (3 premature and 2 term) neonates. Mean Cmin was equal to 91.6 +/- 45.5 ng/ml and higher than C1h (87.4 +/- 43.2 ng/ml), but not significantly. A significant negative correlation was found between Cmin plasma concentration and gestational age as well as with postconceptional age, suggesting that the lower the gestational and postconceptional age, the lower the metoclopramide dosage should be.

Isoniazid acetylation metabolic ratio during maturation in children.

Isoniazid acetylation metabolic ratio (MR) was studied in 61 children with tuberculosis after administration of isoniazid. MR was calculated as the molar acetylisoniazid to isoniazid concentration ratio. MR was used as a probe for N-acetyltransferase activity and to determine the acetylation phenotype. MR had a bimodal distribution with an antimode between 0.48 and 0.77. MR and the percentage of fast acetylators increased significantly with age. The cumulative frequency of fast acetylators increased with age, with a plateau reached around 4 years. MR value was checked during treatment in 44 children. All children but one who initially appeared as fast acetylators remained in this group after repeated testing. Among the 30 slow acetylators, 12 became fast acetylators, and 10 showed a variable phenotyping at different ages. A bimodal distribution of the isoniazid acetylation MR was shown in children, with an antimode close to that described in the literature and a maturation of isoniazid acetylation during the first 4 years.

Pharmacokinetics of the individual enantiomers of vigabatrin in neonates with uncontrolled seizures.

The antiepileptic drug vigabatrin (VGB) is a selective irreversible inhibitor of GABA-transaminase. It is administered as a racemic R(-), S(+) mixture, but the pharmacological activity of vigabatrin resides in the S(+) enantiomer and the R(-) enantiomer is inactive. The pharmacokinetic parameters of the two enantiomers have been studied after administration of a single oral 125 mg dose of the racemate to six neonates. The mean values of Cmax and AUC of the S(+) enantiomer were significantly lower (Cmax: 14.0 +/- 4.3 mg l-1; AUC: 143 +/- 44 mg l-1 h) than those of the R(-) enantiomer (Cmax: 34.1 +/- 9.5 mg l-1; AUC: 231 +/- 88 mg l-1 h), whereas no significant difference in the time to reach Cmax (S(+): 2.1 +/- 1.1 h; R(-): 2.2 +/- 1 h) was observed between the two enantiomers. During chronic administration (125 mg twice daily over 4 days), there was no evidence of accumulation of either enantiomer.

Pharmacokinetics of tiaprofenic acid in infants after a single oral dose.

Ten healthy infants (15.2 +/- 10.6 months old, range 6-35) anesthetized for minor surgery were given a single oral dose (3 mg x kg-1) of tiaprofenic acid (TA). Seven venous blood samples and 0-12 h urine were collected. TA concentrations in plasma and urine were measured by HPLC. Within the whole group the mean +/- SD kinetic parameters were: Cmax: 10.55 +/- 3.31 mg x l-1, Tmax: 1.73 +/- 0.87 h, AUC0-1 32.53 +/- 4.42 mg x l-1 x h, AUC0-infinity 35.33 +/- 4.73 mg x l-1 x h, t1/2 1.82 +/- 0.48 h, Cl/F: 0.09 +/- 0.01 l x h-1 x kg-1, VZ/F: 0.23 +/- 0.08 l x kg-1. Renal clearance was 0.030 +/- 0.009 l x h-1 x kg-1. 32% of the TA dose was recovered in urine, 60% of which was conjugated. AUC0-8h increased significantly with age. The TA kinetic parameters were close to those in 3 to 11-year-old children. The present study suggests slight differences in the TA kinetics between infants and adults. However, the lack of an evidenced direct relationship between plasma TA concentration and either efficacy or tolerance suggests that the TA dose regimen in infants may not have to be different from that in adults.