PO-0934 Comparative Paediatric Acetaminophen Pharmacokinetics Between A Microdose And A Therapeutic Dose Using Accelerator Mass Spectrometry Bioanalysis

ObjectivesWe wished to compare acetaminophen (APAP) paediatric pharmacokinetics (PK) after a therapeutic dose and a microdose. We developed and validated a new approach using Accelerator Mass Spectrometry (AMS) bioanalysis in the 0–2 year old age group.Methods[14C] APAP concentrations in small volume blood samples were measured after enteral or IV administration of a single [14C] APAP microtracer dose as a microdose or incorporated in a therapeutic dose (microtracer with similar PK to the unlabelled APAP).ResultsDose normalised PK parameters AUC0-t, CL and Vss were comparable between a microtracer incorporated in a therapeutic dose and microdose (dose difference approximately 1.5 million fold) when administered either IV or enterally.Abstract PO-0934 Table 1Route Tmax Cmax* AUC0-t*t1/2CL Vss hrmg/Lhr*mg/LhrL/krLIV therapeutic0.93 (1.84)0.16 (0.06)0.54 (0.26)3.78 (3.09)2.72 (3.107.16IV microdose0.47 (0.72)0.30 (0.19)0.84 (0.57)1.69 (0.88)1.76 (1.07)2.55Oral therapeutic1.05 (0.74)0.14 (0.12)0.70 (0.79)2.62 (3.05)2.93 (2.08)8.36Oral microdose0.65 (0.36)0.24 (0.1)0.90 (0.43)1.64 (1.02)1.46 (1.00)2.65Data are mean and s.d. * Cmax and AUC0-t are dose normalised.ConclusionsMicro dosing using AMS bioanalysis is demonstrated to be both possible and practical in the paediatric population. The developed methods may offer ethical, increased bioanalytical sensitivity and safety advantages over dosing regimens used in paediatric PK studies with therapeutic doses.