Relative bioavailability of a paracetamol suppository

Seideman, P; Alván, Gunnar; Andrews, R. S.; Labross, A

doi:10.1007/bf00570165

Cited by 31 publications

(18 citation statements)

References 8 publications

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“…This is in accordance with the results of Seideman et al (5). They found that the bioavailability of suppositories (Panodil 500 mg) was approximately 80% when compared to the corresponding tablet formulation.…”

Section: Resultssupporting

confidence: 82%

Is one paracetamol suppository of 1000 mg bioequivalent with two suppositories of 500 mg

Närvänen

Halsas

Smal

et al. 1998

European Journal of Drug Metabolism and Pharmacokinetics

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A common belief is that one tablet or suppository containing, e.g. 100 mg of a drug can be substituted, without any changes in the therapeutic effect, with two units of the same brand containing 50 mg of the drug. In the present study a single dose of paracetamol was administered to healthy volunteers as (a) two tablets of 500 mg, (b) two suppositories of 500 mg, and (c) one suppository of 1000 mg. There were statistically significant differences in all bioavailability parameters (t(max), C(max) and AUC) between the three treatments. The relative bioavailability of the 500 mg suppositories was 77% and that of the 1000 mg suppositories 66%. The absorption rate from suppositories was markedly lower than from the tablets. Especially low absorption rate was obtained with the suppository of 1000 mg. The two strengths, although having the same trade name, were not therefore bioequivalent.

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Section: Resultssupporting

confidence: 82%

Is one paracetamol suppository of 1000 mg bioequivalent with two suppositories of 500 mg

Närvänen

Halsas

Smal

et al. 1998

European Journal of Drug Metabolism and Pharmacokinetics

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“…Imprecision in paracetamol from this rectal formulation has not been determined. Seideman et al report [34] a relative bioavailability of paracetamol from suppositories of 80% that from oral formulations. In addition, rectal absorption is erratic and variability in bioavailability can range from 24 to 98% (mean 52%) of oral tablets [35].…”

Section: Resultsmentioning

confidence: 99%

Paracetamol plasma and cerebrospinal fluid pharmacokinetics in children

Anderson

Holford

Woollard

et al. 1998

Brit J Clinical Pharma

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Aims Paracetamol has a central action for both antipyresis and analgesia. Maximum temperature decrease and peak analgesia are reported at 1-2 h after peak plasma paracetamol concentration. We wished to determine the relationship between plasma and cerebrospinal fluid (CSF) pharmacokinetics in children. Methods Concentration-time profiles in plasma and CSF after nasogastric paracetamol 40 mg kg −1 were measured in nine children who had indwelling ventricular drains.Estimation of population pharmacokinetic parameters was made using both a standard two-stage population approach (MKMODEL) and a nonlinear mixed effect model (NONMEM). Results were standardized to a 70 kg person using an allometric power model. Results Both approaches gave similar estimates. NONMEM parameter estimates were clearance 10.2 l h −1 (CV 47%), volume of distribution 67.1 l (CV 58%) and absorption rate constant 0.77 h −1 (CV 49%). Cerebrospinal fluid concentrations lagged behind those of plasma. The equilibration half time was 0.72 h (CV 117%). The CSF/plasma partition coefficient was 1.18 (CV 8%). Conclusions Higher concentrations in the CSF probably reflect the lower free water volume of plasma. The CSF equilibration half time suggests that CSF kinetics approximate more closely to the effect compartment than plasma, but further time is required for paracetamol to exert its effects. Effect site concentrations equilibrate slowly with plasma. Paracetamol should be given 1-2 h before anticipated pain or fever in children.

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“…The rectal route has the potential to partially reduce first pass hepatic loss by draining into the inferior and middle haemorrhoidal veins. Bioavailability strongly depends on site of absorption within the rectum [33, 34]. The impact of the rectal venous drainage pattern is questionable, given the degree of rectal venous anastomotic channels, slow absorption times and natural attrition from the rectum.…”

Section: Discussionmentioning

confidence: 99%

A model for size and age changes in the pharmacokinetics of paracetamol in neonates, infants and children

Anderson

Woollard

Holford

2000

Brit J Clinical Pharma

168

104

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Aims The aims of this study were to describe paracetamol pharmacokinetics in neonates and infants. Methods Infants in their ®rst 3 months of life (n=30) were randomised to sequentially receive one of three paracetamol formulations (dose 30±40 mg kg x1 ) over a 2 day period. The formulations were (a) elixir, (b) glycogelatin capsule suppository and (c) triglyceride base suppository. Approximately six blood samples were taken after each dose over the subsequent 10±16 h. Data were analysed using a nonlinear mixed effect model. These neonatal and infant data were then included with data from four published studies of paracetamol pharmacokinetics (n=221) and age-related pharmacokinetic changes investigated. Results Population pharmacokinetic parameter estimates and their coef®cients of variation (CV%) for a one compartment model with ®rst order input, lag time and ®rst order elimination were volume of distribution 69.9 (18%) l and clearance 13.0 (41%) l h x1 (standardized to a 70 kg person). The volume of distribution decreased exponentially with a half-life of 1.9 days from 120 l 70 kg x1 at birth to 69.9 l 70 kg x1 by 14 days. Clearance increased from birth (4.9 l h x1 70 kg x1 ) with a halflife of 3.25 months to reach 12.4 l h x1 70 kg x1 by 12 months. The absorption halflife (t abs ) for the oral preparation was 0.13 (154%) h with a lag time (t lag ) of 0.39 h (31%). Absorption parameters for the triglyceride base and capsule suppositories were t abs 1.34 (90%) h, t lag 0.14 h (31%) and t abs 0.65 (63%) h, t lag 0.54 h (31%), respectively. The t abs for elixir and capsule suppository in children under 3 months were 3.68 and 1.51 times greater than children over 3 months. The relative bioavailability of rectal formulations compared with elixir were 0.67 (30%) and 0.61 (23%) for the triglyceride base and capsule suppositories, respectively. Conclusions Total body clearance of paracetamol at birth is 62% and volume of distribution 174% that of older children. A target concentration above 10 mg l x1 in approximately 50% subjects can be achieved by a dose from 45 mg kg x1 day x1 at birth and up to 90 mg kg x1 day x1 in 5-year-old children. A reduced dose of 75 mg kg x1 day x1 in an 8-year-old child is suf®cient because clearance is a nonlinear function of weight.

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Relative bioavailability of a paracetamol suppository

Cited by 31 publications

References 8 publications

Is one paracetamol suppository of 1000 mg bioequivalent with two suppositories of 500 mg

Is one paracetamol suppository of 1000 mg bioequivalent with two suppositories of 500 mg

Paracetamol plasma and cerebrospinal fluid pharmacokinetics in children

A model for size and age changes in the pharmacokinetics of paracetamol in neonates, infants and children

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