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Background/aims: To investigate the pharmacokinetics of hydroxychloroquine (HCQ) and relationships of HCQ concentration with disease activity variables (concentration-effect relationships) in patients with systemic lupus erythematosus (SLE)., Methods: HCQ concentration and disease activity were measured at a single time point in 60 patients with SLE receiving HCQ for at least 6 months. Some retrospective objective data on disease activity prior to HCQ commencement were available. Correlations were sought between HCQ blood concentrations and disease variables (Systemic Lupus Activity Measure (SLAM) scores, joint scores, morning stiffness, pain, well-being, general improvement, other medication use (including corticosteroids), and physician and patient assessments). Blood HCQ concentrations were also dichotomised into 'more' and 'less/no' disease activity, and mean blood concentrations in the two groups for each disease activity measure were compared., Results: The pharmacokinetics (dose-concentration relationships) of HCQ were highly variable in people with SLE. Apparent total clearance of HCQ from blood was 316 (± 319) mL/min (mean (± standard deviation). There was no correlation between SLAM score, patient global assessment or physician global assessment, and blood HCQ concentrations (r(2) = 0.2, 0.04 and 0.13, respectively; P > 0.05). However, during HCQ therapy, 64% (14 of 22 patients) had a reduction in prednisolone dose of 50% or more compared with pre-HCQ therapy., Conclusions: No significant concentration-effect relationship for HCQ in the treatment of SLE was observed perhaps because consistently high enough blood HCQ concentrations were not achieved. Pharmacokinetic variability led to a wide range of blood HCQ concentrations. A concentration-targeting study for HCQ in SLE would be timely., (© 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.)

Background: A prerequisite for access to biological agents for the treatment of rheumatoid arthritis under Australia's Pharmaceutical Benefits Scheme (PBS) is evidence of an adequate trial of conventional disease-modifying anti-rheumatic drugs (DMARDs). The aim of this study was to examine whether there were changes in prescribing DMARDs since the introduction of the PBS criteria for access to biologicals in August 2003., Methods: A retrospective study was undertaken of the national use of DMARDs in the period before and after the introduction of biologicals under the PBS. Dispensing data were analysed for changes in patterns of DMARD prescription rates (2000-2005)., Results: There were 2 887 746 prescriptions for DMARDs between August 2000 and June 2005. PBS prescriptions accounted for 95% of these. Government expenditure for the DMARDs was $A156m. Trends in the use of DMARDs remained relatively steady over the study period without a significant change around the time the PBS criteria for biologicals were introduced. Use of hydroxychloroquine and leflunomide increased steadily, use of methotrexate and sulfasalazine was stable and use of gold preparations and penicillamine was considerably lower during this 5-year period., Conclusion: Introduction of PBS criteria for access to biologicals did not alter the trends in use of DMARDs based on national dispensing data. This study emphasized the value that would accrue from availability of more comprehensive, de-identified, individual patient data that would enable more detailed examination of the use of medicines. These data are available, but cannot be easily accessed. It is time to make the data available for approved, ethical research in the interests of better outcomes from medicines supplied under PBS.

We describe the progress towards developing a patient rated toxicity index that meets all of the patient-important attributes defined by the OMERACT Drug Safety Working Party. These attributes are frequency, severity, importance to patient, importance to the clinician, impact on economics, impact on activities, and integration of adverse effects with benefits. The Stanford Toxicity Index (STI) has been revised to collect all attributes with the exception of impact on activities. However, since the STI is a part of the Health Assessment Questionnaire (HAQ), impact on activities is collected by the HAQ. In particular, a new question asks patients to rate overall satisfaction, taking into consideration both benefits and adverse effects. The next step in the development of this tool is to ensure that the STI meets the OMERACT filter of truth, discrimination, and feasibility. Although truth and feasibility have been confirmed by comparisons within the ARAMIS database, discrimination needs to be assessed in clinical trials.

Drugs administered as therapy for rheumatological disorders are a relatively common cause of adverse events. Important data regarding the effects of drugs on patients with rheumatological conditions is being lost or rendered inaccessible because of deficiencies in classification, measurement, and collection methods for adverse drug reactions. A significant number of adverse reactions to drugs will not be known before marketing, and hence vigilance on the part of clinicians and patients in observing and documenting these reactions is paramount in building our knowledge and modifying our practice accordingly. A variety of systems and methods for detecting adverse drug reactions are described, critically evaluated, and compared for cost, potential bias, ethical concerns, and subject recruitment required for necessary statistical power. Systems need to be developed to give access to the wealth of clinical experimental data available in the individual practices of a broad spectrum of clinicians. To facilitate this, representative organizations need to make adverse drug reactions a high priority as well as contributing expertise and finance to database formulation and accessibility.

1. Nine healthy subjects each received three doses of 155 mg rac-hydroxychloroquine, as a tablet, an oral solution and by intravenous infusion, in a randomised cross-over design study, 30 min after a standard high fat breakfast. 2. Four methods of deconvolution were used to assess the absolute bioavailability of the tablet and oral solution doses. These were the delta function method, the staircase approximation method, and two least squares methods using a single first-order input and a sequential first-order input. The mean (+/- s.d.) fraction absorbed estimated by the four methods was 0.64 +/- 0.14 after the tablet and 0.87 +/- 0.30 after the oral solution. Wide intersubject variability was observed (0.50-0.91 for the tablet; 0.30-1.37 for the solution). 3. The mean (+/- s.d.) absorption half-life was 3.7 +/- 2.0 h for the tablet and 3.3 +/- 1.6 h for the solution, suggesting that absorption following the tablet dose was not rate-limited by dissolution. 4. The in vivo dissolution rate, extent of release and lag-time were determined using cube-root law and first-order input functions. Dissolution was found to be rapid, after a significant lag-time, but incomplete in some subjects. 5. The rate and extent of absorption was similar to that reported previously for fasted subjects. The lag-time before absorption commenced in fed subjects (1.65 +/- 0.46 h) showed a significant three-fold increase over that reported previously in fasting subjects (0.63 +/- 0.33 h), but this difference is not likely to be of clinical significance.