Australian public assessment for Ibuprofen - Therapeutic Goods ...

AusPAR Caldolor Ibuprofen Phebra Pty Ltd PM-2010-02393-3-1
Final 2 January 2013
Therapeutic Goods Administration
Summary pharmacokinetic results from CPI-CL-004, stratified according to illness
severity, are shown in the following tables.
Table 4. CPI-CL-004: Summary pharmacokinetic results (mean).
Dosage (mg q4h),
Illness stratum
n AUC 0-4h AUC 0-4h
Dose 1
C max t max C min t min t 1/2
/Dose
(µg.h/mL) (µg/mL) (h) (µg/mL) (h) (h)
100 A: Critical 9 ‡ 16.1 161 8.2 0.6 2.2 4.0 2.42
B: Non-Critical 14 † 26.3 263 14.5 0.5 2.9 4.0 2.49
Ratio * - 0.61 0.61 0.57 - 0.76 - -
200 A: Critical 9 19.6 98 11.5 0.5 2.3 3.8 2.56
B: Non-Critical 17 § 39.5 198 22.9 0.5 4.7 3.9 1.86
Ratio * - 0.50 0.49 0.50 - 0.49 - -
400 A: Critical 10 # 45.9 115 25.7 0.5 4.7 3.9 2.32
B: Non-Critical 15 $ 87.1 217 49.1 0.5 10.7 3.8 2.22
Ratio * - 0.53 0.53 0.52 - 0.44 - -
*Critical/Non-critical, calculated by evaluator. ‡n=6 for t 1/2 . †n=15 for C max and tmax. ‡n=16 for t 1/2 . #n=9 for t 1/2 . $n=14
for t 1/2
Table 5. CPI-CL-004: Trough ibuprofen concentrations (mean).
Dosage (mg q4h),
Illness stratum
n Dose 1 Dose 6 Ratio *
C 4h C 0h C 4h C 0h(Dose 6) /
(μg/mL) (μg/mL) (μg/mL)
C 4h(Dose 1)
C 4h(Dose 6) /
C 4h(Dose 1)
100 Critical 9 2.2 3.8 2.6 1.7 1.2
Non-Critical 15 2.9 4.6 4.4 1.6 1.5
200 Critical 9 3.1 4.0 2.7 1.3 0.9
Non-Critical 17 4.8 6.4 5.2 1.3 1.1
400 Critical 10 6.8 8.1 8.2 1.2 1.2
Non-Critical 15 11.8 14.3 11.3 1.2 1.0
*Calculated by evaluator.
Peak and trough ibuprofen concentrations and systemic exposure were markedly lower in
critically ill patients than in non-critically ill patients, although the pharmacokinetics
remained first order in both patient groups. The reason for the difference is not known.
Importantly, the elimination half-life of ibuprofen did not differ between critically ill and
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