Pharmacokinetics of oral and rectal flurbiprofen in children

Scaroni, Carla; Mazzoni, P; D’Amico, Emanuele; Benvenuti, Claudio; Hind, I. D.

doi:10.1007/bf00542178

Cited by 14 publications

(13 citation statements)

References 4 publications

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“…Our results agree with those of the earlier flurbiprofen study in eight children aged 6–12 years [3] in which a mean V d / F of 0.15 l kg −1 for oral syrup was estimated. This is very close to our estimate of 0.14 l kg −1 at steady state, when bioavailability ( F ) is taken into account.…”

Section: Discussionsupporting

confidence: 92%

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Plasma and cerebrospinal fluid pharmacokinetics of flurbiprofen in children

Kumpulainen

Välitalo

Kokki

et al. 2010

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTFlurbiprofen is a commonly used non-steroidal anti-inflammatory drug in children to treat pain and fever. There is limited information on the pharmacokinetics of flurbiprofen in children and no data on the cerebrospinal fluid permeation of flurbiprofen. WHAT THIS STUDY ADDSOur population pharmacokinetic model indicates that weight-based dosing of flurbiprofen is appropriate in children older than 6 months. The bioavailability of oral flurbiprofen syrup is high, 71-91%, and thus, the oral syrup provides accurate dosing in paediatric patients. Cerebrospinal fluid concentrations of flurbiprofen are markedly higher than the unbound plasma concentrations. AIMSThis study was designed to characterize paediatric pharmacokinetics and central nervous system exposure of flurbiprofen. METHODSThe pharmacokinetics of flurbiprofen were studied in 64 healthy children aged 3 months to 13 years, undergoing surgery with spinal anaesthesia. Children were administered preoperatively a single dose of flurbiprofen intravenously as prodrug (n = 27) or by mouth as syrup (n = 37). A single cerebrospinal fluid (CSF) sample (n = 60) was collected at the induction of anaesthesia, and plasma samples (n = 304) before, during and after the operation (up to 20 h after administration). A population pharmacokinetic model was built using the NONMEM software package. RESULTSFlurbiprofen concentrations in plasma were well described by a three compartment model. The apparent bioavailability of oral flurbiprofen syrup was 81%. The estimated clearance (CL) was 0.96 l h -1 70 kg -1 . Age did not affect the clearance after weight had been included as a covariate. The estimated volume of distribution at steady state (Vss) was 8.1 l 70 kg -1. Flurbiprofen permeated into the CSF, reaching concentrations that were seven-fold higher compared with unbound plasma concentrations. CONCLUSIONSFlurbiprofen pharmacokinetics can be described using only weight as a covariate in children above 6 months, while more research is needed in neonates and in younger infants.

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Section: Discussionsupporting

confidence: 92%

“…For the second group (mean weight 33.9 kg), the mean CL/ F was 1.11 l h −1 , which is higher than our estimate of 0.68 l h −1 . The disparity likely results from two relatively high individual CL/ F values observed in the previous study [3].…”

Section: Discussionmentioning

confidence: 61%

Plasma and cerebrospinal fluid pharmacokinetics of flurbiprofen in children

Kumpulainen

Välitalo

Kokki

et al. 2010

Brit J Clinical Pharma

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“…Close similarities between the pharmacokinetic characteristics, including bioavailability, in paediatric volunteers given flurbiprofen as suppositories and syrup have been demonstrated (table IV).f 23 ] …”

Section: Influence Of Age On Pharmacokineticsmentioning

confidence: 73%

Clinical Pharmacokinetics of Flurbiprofen and its Enantiomers

Davies

1995

Clinical Pharmacokinetics

129

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Flurbiprofen is a chiral nonsteroidal anti-inflammatory drug (NSAID) of the 2-arylpropionic acid class. Although it possesses a chiral centre, with the S-(+)-enantiomer possessing most of the beneficial anti-inflammatory activity, both enantiomers may possess analgesic activity and all flurbiprofen preparations to date are marketed as the racemate. Flurbiprofen exhibits stereoselectivity in its pharmacokinetics. Stereoselectivity is exhibited at the level of protein binding and metabolite formation. Hence, the data generated using nonstereoselective assays may not be used to explain the pharmacokinetics of individual enantiomers. The absorption of flurbiprofen is rapid and almost complete when given orally. The area under the plasma concentration-time curve of flurbiprofen is proportional to the dose administered to patients. Sustained release dosage forms are available, which may be beneficial due to the short terminal phase elimination half-life of conventional immediate release flurbiprofen (3 to 6 hours). They may also decrease local gastrointestinal adverse effects. Although with these preparations the peak plasma drug concentration is reduced and time taken to achieve peak concentrations is prolonged, the bioavailability is the same as that with regular release counterparts. Flurbiprofen binds extensively to plasma albumin, apparently in a stereoselective manner. Substantial concentrations of the drug are attained in synovial fluid, which is the proposed site of action of NSAIDs. There is negligible R to S inversion after oral administration. Flurbiprofen is eliminated following extensive biotransformation to glucuro-conjugated metabolites. Conjugates are excreted in urine, and approximately 20% of flurbiprofen is eliminated unchanged. The excretion of conjugates may be tied to renal function as accumulation of conjugates occurs in end-stage renal disease, but not in young individuals or elderly patients. Although flurbiprofen is excreted into breast milk, the amount of drug transferred comprises only a small fraction of the maternal exposure. Significant drug interactions have been demonstrated for aspirin (acetylsalicylic acid), coumarins and propranolol. The relationship between concentration and anti-inflammatory and analgesic effect has yet to be elucidated for this drug.

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“…This agent has undergOile limited pharmacokinetic evaluation in healthy children (6 to 8 years old, bodyweight 18.6 ± 3.6kg), with results similar to those found in adults (Scaroni et al 1984). The drug is absorbed rapidly and almost completely, the rate of absorption being formulation dependent.…”

Section: F1urbiprofenmentioning

confidence: 66%

Clinical Pharmacokinetics of Drugs Used in Juvenile Arthritis

Skeith

Jamali

1991

Clinical Pharmacokinetics

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Juvenile arthritis is defined as the occurrence of objective evidence of arthritis for a minimum of 6 weeks, in a child 16 years of age or younger. With a reported incidence of 9 to 19.6 per 100,000 children, juvenile arthritis is considered to be a rare disease. There is no known cure; however, up to 75% of patients will undergo remission by late adolescence. Drugs used in the treatment of juvenile arthritis are divided into 2 major classes: (a) the nonsteroidal anti-inflammatory drugs (NSAIDs) including salicylates, naproxen, ibuprofen, fenoprofen, ketoprofen, flurbiprofen, indomethacin, sulindac, tolmetin and diclofenac, and (b) disease modifying agents which encompass drugs such as antimalarial agents, gold, methotrexate, penicillamine and sulfasalazine. In almost all the reports dealing with the pharmacokinetics of NSAIDs, the level of disease activity has not been noted. The level of activity is important since, during a flare, the plasma albumin may fall to the point that it causes a substantial and clinically significant increase in the unbound serum concentration of highly bound drugs. The relationship between the concentration of these drugs in the systemic circulation and their efficacy is not clear. However, for many of them, therapeutic drug monitoring is recommended as a means of reducing the possibility of toxic reactions. Further pharmacokinetic and -dynamic evaluations are needed for many of these drugs in juvenile arthritis.

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Pharmacokinetics of oral and rectal flurbiprofen in children

Cited by 14 publications

References 4 publications

Plasma and cerebrospinal fluid pharmacokinetics of flurbiprofen in children

Plasma and cerebrospinal fluid pharmacokinetics of flurbiprofen in children

Clinical Pharmacokinetics of Flurbiprofen and its Enantiomers

Clinical Pharmacokinetics of Drugs Used in Juvenile Arthritis

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