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

Abstract

<sec><st>Objectives</st> We 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. </sec> <sec><st>Methods</st> [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). </sec> <sec><st>Results</st> Dose normalised PK parameters AUC<inf>0-t</inf>, CL and V<inf>ss</inf> 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. <tbl id="T1" loc="float"><no>Abstract PO-0934 Table 1</no><tblbdy><r><c cspan="1" rspan="1"> <b>Route </b> </c><c cspan="1" rspan="1"> <b>Tmax </b> </c><c cspan="1" rspan="1"> <b>C<inf>max</inf>* </b> </c><c cspan="1" rspan="1"> <b>AUC<inf>0-t</inf>*</b> </c><c cspan="1" rspan="1"> <b>t<inf>1/2</inf> </b> </c><c cspan="1" rspan="1"> <b>CL </b> </c><c cspan="1" rspan="1"> <b>V<inf>ss</inf> </b> </c></r><r><c cspan="1" rspan="1"> </c><c cspan="1" rspan="1"> <b>hr</b> </c><c cspan="1" rspan="1"> <b>mg/L</b> </c><c cspan="1" rspan="1"> <b>hr*mg/L</b> </c><c cspan="1" rspan="1"> <b>hr</b> </c><c cspan="1" rspan="1"> <b>L/kr</b> </c><c cspan="1" rspan="1"> <b>L</b> </c></r><r><c cspan="1" rspan="1">IV therapeutic</c><c cspan="1" rspan="1">0.93 (1.84)</c><c cspan="1" rspan="1">0.16 (0.06)</c><c cspan="1" rspan="1">0.54 (0.26)</c><c cspan="1" rspan="1">3.78 (3.09)</c><c cspan="1" rspan="1">2.72 (3.10</c><c cspan="1" rspan="1">7.16</c></r><r><c cspan="1" rspan="1">IV microdose</c><c cspan="1" rspan="1">0.47 (0.72)</c><c cspan="1" rspan="1">0.30 (0.19)</c><c cspan="1" rspan="1">0.84 (0.57)</c><c cspan="1" rspan="1">1.69 (0.88)</c><c cspan="1" rspan="1">1.76 (1.07)</c><c cspan="1" rspan="1">2.55</c></r><r><c cspan="1" rspan="1">Oral therapeutic</c><c cspan="1" rspan="1">1.05 (0.74)</c><c cspan="1" rspan="1">0.14 (0.12)</c><c cspan="1" rspan="1">0.70 (0.79)</c><c cspan="1" rspan="1">2.62 (3.05)</c><c cspan="1" rspan="1">2.93 (2.08)</c><c cspan="1" rspan="1">8.36</c></r><r><c cspan="1" rspan="1">Oral microdose</c><c cspan="1" rspan="1">0.65 (0.36)</c><c cspan="1" rspan="1">0.24 (0.1)</c><c cspan="1" rspan="1">0.90 (0.43)</c><c cspan="1" rspan="1">1.64 (1.02)</c><c cspan="1" rspan="1">1.46 (1.00)</c><c cspan="1" rspan="1">2.65</c></r></tblbdy><tblfn> Data are mean and s.d. * C<inf>max</inf> and AUC<inf>0-t</inf> are dose normalised. </tblfn></tbl> </sec> <sec><st>Conclusions</st> Micro 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. </sec>