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Background and ObjectiveSeveral features favor paracetamol (acetaminophen) administration by the intravenous rather than the oral route in the postoperative setting. This study compared the pharmacokinetics and bioavailability of oral and intravenous paracetamol when given with or without an opioid, morphine.MethodsIn this randomized, single-blind, parallel, repeat-dose study in healthy adults, subjects received four repeat doses of oral or intravenous 1000 mg paracetamol at 6-h intervals, and morphine infusions (0.125 mg/kg) at the 2nd and 3rd intervals. Comparisons of plasma pharmacokinetic profiles were conducted before, during, and after opioid co-administrations.ResultsTwenty-two subjects were included in the pharmacokinetic analysis. Observed paracetamol peak concentration (C max) and area under the plasma concentration-time curve over the dosing interval (AUC0–6) were reduced when oral paracetamol was co-administered with morphine (reduced from 11.6 to 7.25 µg/mL and from 31.00 to 25.51 µg·h/mL, respectively), followed by an abruptly increased C max and AUC0–6 upon discontinuation of morphine (to 13.5 µg/mL and 52.38 µg·h/mL, respectively). There was also a significantly prolonged mean time to peak plasma concentration (T max) after the 4th dose of oral paracetamol (2.84 h) compared to the 1st dose (1.48 h). However, pharmacokinetic parameters of paracetamol were not impacted when intravenous paracetamol was co-administered with morphine.ConclusionsMorphine co-administration significantly impacted the pharmacokinetics of oral but not intravenous paracetamol. The abrupt release of accumulated paracetamol at the end of morphine-mediated gastrointestinal inhibition following oral but not intravenous administration of paracetamol suggests that intravenous paracetamol provides a better option for the management of postoperative pain.ClinicalTrials.gov IdentifierNCT02848729.

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This article seeks to examine whether and how a non-standard variety of English (i.e. Singlish) might contribute to (dis)affiliation amongst a multinational group of academically elite students in Singapore. Using interview data when informants expressed ideologies about Singlish and Standard English, I argue that informants tended to orient to two different social fields in interviews: a field of education where Standard English is consistently valued by them, and an informal field of socialisation where the value of Singlish is contested. Differences in valuation of Singlish suggest disaffiliation between two groups of academically elite students: (a) immigrants from China who arrived more recently and do not value Singlish; (b) localised peer groups (including immigrants and Singaporeans) who claim to value and practise Singlish in their informal interactions. There are implications for our understanding of the role of vernaculars in processes of transnational migration, and Singlish as a local marker of solidarity.

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