Pharmacokinetics and tolerance of flunitrazepam in neonates and in infants

Pariente-Khayat, Ann; Tréluyer, Jean‐Marc; Rey, Elisabeth; Mokhtari, Mostafa; Werner, E.; Jouvet, Philippe; d'Athis, P; Wood, Christopher; Hubert, Philippe; HOTELLIER, F

doi:10.1053/cp.1999.v66.100596001

Cited by 4 publications

(1 citation statement)

References 9 publications

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“…These changes will result in a relatively higher volume of distribution of water-soluble drugs in childhood than in adulthood. The volume of distribution of liposoluble drugs such as diazepam and flunitrazepam is smaller in neonates and very young infants than in adults [9,52,53]. The volume of distribution of sufisoxazole in neonates is twice that in adults [6].…”

Section: Body Watermentioning

confidence: 99%

Drug metabolism and disposition in children

Benedetti

Baltes

2003

Fundamemntal Clinical Pharma

153

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Key factors undergoing maturational changes accounting for differences in drug metabolism and disposition in the pediatric population compared with adults are reviewed. Gastric and duodenal pH, gastric emptying time, intestinal transit time, bacterial colonization and probably P-glycoprotein are important factors for drug absorption, whereas key factors explaining differences in drug distribution between the pediatric population and adults are membrane permeability, plasma protein concentration and plasma protein characteristics, endogenous substances in plasma, total body and extracellular water, fat content, regional blood flow and probably P-glycoprotein, mainly that present in the gut, liver and brain. As far as drug metabolism is concerned, important differences have been found in the pediatric population compared with adults both for phase I enzymes [oxidative (e.g. cytochrome CYP3A7 vs. CYP3A4 and CYP1A2), reductive and hydrolytic enzymes] and phase II enzymes (e.g. N-methyltransferases and glucuronosyltransferases). Finally, key factors undergoing maturational changes accounting for differences in renal excretion in the pediatric population compared with adults are glomerular filtration and tubular secretion. It would be important to generate information on the developmental aspects of renal P-glycoprotein and of other renal transporters as done and still being done with the different isozymes involved in drug metabolism.

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Section: Body Watermentioning

confidence: 99%

Drug metabolism and disposition in children

Benedetti

Baltes

2003

Fundamemntal Clinical Pharma

153

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Pharmacokinetics and Therapeutic Drug Monitoring of Psychotropic Drugs in Pediatrics

Pichini¹,

Papaseit²,

Joya³

et al. 2009

Therapeutic Drug Monitoring

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Therapeutic drug monitoring (TDM) in pediatrics (0-14 years) is especially important because the absorption, distribution, metabolism, and excretion of drugs and drug pharmacokinetic profiles can be different from that of the adult population. In this context, several parameters like half-life of drug elimination from the body (t(1/2)), peak plasma concentration (Cmax), area under the curve, clearance (CL), Tmax, and dose/concentration relationship in children may differ from adults. Hence, the knowledge of pharmacokinetic parameters and therapeutic and toxic ranges of drug concentrations may help the clinicians to optimize drug treatment regimens in the pediatric population. TDM of psychotropic drugs requires particular attention for the pharmacological and clinical consequences of nonadequate dose use, lack in the compliance, and overdoses with possible toxic effects. Psychoactive drugs such as benzodiazepines, antiepileptic drugs, tricyclic antidepressants, selective serotonin reuptake inhibitors, antipsychotic drugs, psychostimulants (attention-deficit hyperactivity disorder drugs), opioid analgesics, and antimigraine drugs are a heterogeneous group. These drugs are subject to interindividual variability, and therefore, the usefulness of TDM for these drugs has to be assessed individually. Because of the occurrence of comorbid pathologies, including psychiatric disorders, the use of combined pharmacotherapy is not uncommon. As a consequence, these patients may be at risk from a number of potential drug-drug interactions. The implementation of TDM in pediatric population is more difficult than in adults because some sampling procedures are invasive and cause discomfort in children, and additionally, they require the cooperation of the patient. Several examples will be provided where the use of alternative matrices, such as saliva, is proposed to minimize inconvenience and patient discomfort.

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Scientific and Regulatory Considerations for Studies in Special Populations

Sahajwalla¹

2004

Drugs and the Pharmaceutical Sciences

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Pharmacokinetics and tolerance of flunitrazepam in neonates and in infants

Abstract: Postnatal age but not gestational age influenced flunitrazepam pharmacokinetic parameters in neonates and infants. Diastolic blood pressure was inversely correlated to flunitrazepam plasma concentration.

Cited by 4 publications

References 9 publications

Drug metabolism and disposition in children

Drug metabolism and disposition in children

Pharmacokinetics and Therapeutic Drug Monitoring of Psychotropic Drugs in Pediatrics

Scientific and Regulatory Considerations for Studies in Special Populations

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