Abstract
To determine the pharmacokinetics (PK) of a new i.v. formulation of paracetamol (Perfalgan) in children 15 yr of age.
After obtaining written informed consent, children under 16 yr of age were recruited to this study. Blood samples were obtained at 0, 15, 30 min, 1, 2, 4, 6, and 8 h after administration of a weight-dependent dose of i.v. paracetamol. Paracetamol concentration was measured using a validated high-performance liquid chromatographic assay with ultraviolet detection method, with a lower limit of quantification (LLOQ) of 900 pg on column and an intra-day coefficient of variation of 14.3 at the LLOQ. Population PK analysis was performed by non-linear mixed-effect modelling using NONMEM.
One hundred and fifty-nine blood samples from 33 children aged 1.815 yr, weight 13.756 kg, were analysed. Data were best described by a two-compartment model. Only body weight as a covariate significantly improved the goodness of fit of the model. The final population models for paracetamol clearance (CL), V-1 (central volume of distribution), Q (inter-compartmental clearance), and V-2 (peripheral volume of distribution) were: 16.51(WT/70)(0.75), 28.4(WT/70), 11.32(WT/70)(0.75), and 13.26(WT/70), respectively (CL, Q in litres per hour, WT in kilograms, and V-1 and V-2 in litres).
In children aged 1.815 yr, the PK parameters for i.v. paracetamol were not influenced directly by age but were by total body weight and, using allometric size scaling, significantly affected the clearances (CL, Q) and volumes of distribution (V-1, V-2).
| Original language | English |
|---|---|
| Pages (from-to) | 823-829 |
| Number of pages | 7 |
| Journal | British Journal of Anaesthesia |
| Volume | 108 |
| Issue number | 5 |
| Early online date | 1 Mar 2012 |
| DOIs | |
| Publication status | Published - May 2012 |
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Keywords
- children
- intravenous
- paracetamol
- pharmacokinetics
- acetaminophen pharmacokinetics
- IV paracetemol
- propacetamol
- chlorzoxazone
- clearance
- tolerance
- obesity
- humans
- CYP2E1
- size
Cite this
Population pharmacokinetics of single-dose intravenous paracetamol in children. / Mohammed, B. S.; Engelhardt, T.; Cameron, G. A.; Cameron, L.; Hawksworth, G. M.; Hawwa, A. F.; McElnay, J.; Helms, P. J.; McLay, J. S.
In: British Journal of Anaesthesia, Vol. 108, No. 5, 05.2012, p. 823-829.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Population pharmacokinetics of single-dose intravenous paracetamol in children
AU - Mohammed, B. S.
AU - Engelhardt, T.
AU - Cameron, G. A.
AU - Cameron, L.
AU - Hawksworth, G. M.
AU - Hawwa, A. F.
AU - McElnay, J.
AU - Helms, P. J.
AU - McLay, J. S.
PY - 2012/5
Y1 - 2012/5
N2 - To determine the pharmacokinetics (PK) of a new i.v. formulation of paracetamol (Perfalgan) in children 15 yr of age.After obtaining written informed consent, children under 16 yr of age were recruited to this study. Blood samples were obtained at 0, 15, 30 min, 1, 2, 4, 6, and 8 h after administration of a weight-dependent dose of i.v. paracetamol. Paracetamol concentration was measured using a validated high-performance liquid chromatographic assay with ultraviolet detection method, with a lower limit of quantification (LLOQ) of 900 pg on column and an intra-day coefficient of variation of 14.3 at the LLOQ. Population PK analysis was performed by non-linear mixed-effect modelling using NONMEM.One hundred and fifty-nine blood samples from 33 children aged 1.815 yr, weight 13.756 kg, were analysed. Data were best described by a two-compartment model. Only body weight as a covariate significantly improved the goodness of fit of the model. The final population models for paracetamol clearance (CL), V-1 (central volume of distribution), Q (inter-compartmental clearance), and V-2 (peripheral volume of distribution) were: 16.51(WT/70)(0.75), 28.4(WT/70), 11.32(WT/70)(0.75), and 13.26(WT/70), respectively (CL, Q in litres per hour, WT in kilograms, and V-1 and V-2 in litres).In children aged 1.815 yr, the PK parameters for i.v. paracetamol were not influenced directly by age but were by total body weight and, using allometric size scaling, significantly affected the clearances (CL, Q) and volumes of distribution (V-1, V-2).
AB - To determine the pharmacokinetics (PK) of a new i.v. formulation of paracetamol (Perfalgan) in children 15 yr of age.After obtaining written informed consent, children under 16 yr of age were recruited to this study. Blood samples were obtained at 0, 15, 30 min, 1, 2, 4, 6, and 8 h after administration of a weight-dependent dose of i.v. paracetamol. Paracetamol concentration was measured using a validated high-performance liquid chromatographic assay with ultraviolet detection method, with a lower limit of quantification (LLOQ) of 900 pg on column and an intra-day coefficient of variation of 14.3 at the LLOQ. Population PK analysis was performed by non-linear mixed-effect modelling using NONMEM.One hundred and fifty-nine blood samples from 33 children aged 1.815 yr, weight 13.756 kg, were analysed. Data were best described by a two-compartment model. Only body weight as a covariate significantly improved the goodness of fit of the model. The final population models for paracetamol clearance (CL), V-1 (central volume of distribution), Q (inter-compartmental clearance), and V-2 (peripheral volume of distribution) were: 16.51(WT/70)(0.75), 28.4(WT/70), 11.32(WT/70)(0.75), and 13.26(WT/70), respectively (CL, Q in litres per hour, WT in kilograms, and V-1 and V-2 in litres).In children aged 1.815 yr, the PK parameters for i.v. paracetamol were not influenced directly by age but were by total body weight and, using allometric size scaling, significantly affected the clearances (CL, Q) and volumes of distribution (V-1, V-2).
KW - children
KW - intravenous
KW - paracetamol
KW - pharmacokinetics
KW - acetaminophen pharmacokinetics
KW - IV paracetemol
KW - propacetamol
KW - chlorzoxazone
KW - clearance
KW - tolerance
KW - obesity
KW - humans
KW - CYP2E1
KW - size
U2 - 10.1093/bja/aes025
DO - 10.1093/bja/aes025
M3 - Article
VL - 108
SP - 823
EP - 829
JO - British Journal of Anaesthesia
JF - British Journal of Anaesthesia
SN - 0007-0912
IS - 5
ER -