Mass or molar? Recommendations for reporting concentrations of therapeutic drugs.

A working party (WP) from the Australasian Association of Clinical Biochemists, Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, Royal College of Pathologists of Australasia and Royal Australasian College of Physicians recommends the following: *mass units should be used for reporting therapeutic drug concentrations in Australia and New Zealand; and the litre (L) should be used as the denominator when expressing concentration. Examples of these units are mg/L and µg/L Exceptions to these principles include: *drugs for which there is current uniformity of reporting and supporting information using molar units, notably lithium (mmol/L) and methotrexate (µmol/L); *drugs that are also present as endogenous substances, where the units used routinely should continue to be used. This applies to many substances, including minerals (eg, iron; µmol/L), vitamins (eg, vitamin D; nmol/L) and hormones (eg, thyroxine; pmol/L). *drugs for which the denominator is not a 198 of fluid and there is international uniformity of reporting (eg, thiopurine metabolites; per 109 red blood cells). These recommendations relate to drugs that are used therapeutically, whether measured for therapeutic drug monitoring purposes or for assessment of overdose. Other substances, such as drugs of misuse, heavy metals or environmental toxins, were not considered by the WP and are thus not covered by this document. These recommendations should also be applied to other supporting documentation such as published guidelines, journal articles and websites. The implementation of these recommendations in New Zealand is subject to local confirmation.

Stability and tolerability of high concentrations of intrathecal bupivacaine and opioid mixtures in chronic noncancer pain: an open-label pilot study.

OBJECTIVE: To evaluate the stability and tolerability of high concentrations of bupivacaine-opioid solutions when used by intrathecal infusion. DESIGN: Prospective, open label, pilot cohort study. SETTING: Outpatients at a University medical center. PATIENTS: Twelve patients with inadequate pain control already receiving intrathecal opioids and low dose bupivacaine. INTERVENTIONS: Increasing concentrations and doses of bupivacaine between 1 and 5% were prescribed to be added to a stable daily opioid dose. Drug infusate sampling and analysis using high performance liquid chromatography. OUTCOME MEASURES: Physical examination, assessment of pain and function between (0-60 days) using a linear visual analog scale, and the Oswestry Disability Index. RESULTS: Final daily doses of bupivacaine were 4-21.4 mg delivered at measured concentrations of 0.4-3.7%. Two patients experienced reversible motor weakness at 6 mg of bupivacaine/day. The in vitro and in vivo sampling of concentrations up to 3.7% of bupivacaine demonstrated that the stability for bupivacaine with morphine (1.2-3%) or hydromorphone (0.4-1%) was >96% of the manufactured concentration. There were no clinically significant changes in the visual analog pain scale or the Oswestry Disability Index. CONCLUSIONS: This in vivo study demonstrates excellent stability of high concentrations of intrathecal bupivacaine and opioid mixtures. No nonreversible neurological complications were identified in patients receiving daily doses of bupivacaine up to 21.4 mg. Tolerability was variable because of motor weakness. Given that all intrathecal local anesthetics may be neurotoxic, caution must be exercised if high concentrations and daily doses are to be delivered over prolonged periods.