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Previous studies suggest that estimated creatinine clearance, the conventional measure of renal function, does not adequately reflect changes in renal drug handling in some patients, including the immunosuppressed. The aim of this study was to develop and validate a cocktail of markers, to be given in a single administration, capable of detecting alterations in the renal elimination pathways of glomerular filtration, tubular secretion and tubular reabsorption.
Healthy male subjects (n = 12) received intravenously infused 2500 mg sinistrin (glomerular filtration) and 440 mg p-aminohippuric acid (PAH; anion secretion), and orally administered 100 mg fluconazole (reabsorption) and 15 mg rac-pindolol (cation secretion). The potential interaction between these markers was investigated in a pharmacokinetic study where markers (M) or fluconazole (F) were administered alone or together (M + F). Validated analytical methods were used to measure plasma and urine concentrations in order to quantify the renal handling of each marker. Plasma protein binding of fluconazole was measured by ultrafiltration. All subjects had an estimated creatinine clearance within the normal range. The renal clearance of each marker (mean±s.d.) was calculated as the ratio of the amount excreted in urine and the area-under-the-concentration-time curve. Statistical comparisons were made using a paired t-test and 95% confidence intervals were reported.
The renal clearances of sinistrin (M: 119 ± 31 ml min−1; M + F: 130 ± 40 ml min−1; P = 0.32), PAH (M: 469 ± 145 ml min−1; M + F: 467 ± 146 ml min−1; P = 0.95), R-pindolol (M: 204 ± 41 ml min−1; M + F: 190 ± 41 ml min−1; P = 0.39; n = 11), S-pindolol (M: 225 ± 55 ml min−1; M + F: 209 ± 60 ml min−1; P = 0.27; n = 11) and fluconazole (F: 14.9 ± 3.8 ml min−1; M + F: 13.6 ± 3.4 ml min−1; P = 0.16) were similar when the markers or fluconazole were administered alone (M or F) or as a cocktail (M + F).
This study found no interaction between markers and fluconazole in healthy male subjects, suggesting that a single administration of this cocktail of markers of different renal processes can be used to simultaneously investigate pathways of renal drug elimination.
creatinine clearance, fluconazole, pindolol, renal drug elimination, tubular reabsorption, tubular secretion
Simultaneous administration of a cocktail of markers to measure renal drug elimination pathways: absence of a pharmacokinetic interaction between fluconazole and sinistrin, p-aminohippuric acid and pindolol
A S Gross,1,* A J McLachlan,2 I Minns,1 J B Beal,3 and S E Tett3
Using a Theory of Planned Behavior (TPB) framework the current study explored the beliefs of current blood donors (N = 172) about donating during a low and high-risk phase of a potential avian influenza outbreak. While the majority of behavioral, normative, and control beliefs identified in preliminary research differed as a function of donors’ intentions to donate during both phases of an avian influenza outbreak, regression analyses suggested that the targeting of different specific beliefs during each phase of an outbreak would yield most benefit in bolstering donors’ intentions to remain donating. The findings provide insight in how to best motivate donors in different phases of an avian influenza outbreak.
Avian influenza, Theory of Planned Behavior
Beliefs underlying blood donors’ intentions to donate during two phases of an avian influenza outbreak
Barbara M. Masser,a,⁎ Katherine M. White,b,c Kyra Hamilton,b,c and Blake M. McKimmiea
This study evaluated the use of and need for opioids in patients attending the Multidisciplinary Pain Centre at the Royal Brisbane Hospital (RBH).
All consecutive in-patient admissions in 1998 were reviewed. A 10-point scoring system based on the World Health Organization (WHO) analgesic ladder was devised to facilitate comparison of analgesic prescribing on admission and at the time of discharge. A conversion table was used to standardize opioid analgesic doses to an oral morphine equivalent.
Of the 370 patients reviewed, 233 (81%) were by their general practitioners. Records of 288 (78%) were available for full review and 270 (94%) of these had noncancer pain. On admission, 239 (83%) were taking an opioid analgesic, with 135 (47%) taking strong opioids (e.g. morphine, oxycodone, methadone). There was a significant decrease in the mean total daily oral morphine equivalent prescribed on discharge 36.9 mg (95% CI: 33.4, 40.4) compared with that on admission 88.7 mg (95% CI: 77.6, 99.8) (P < 0.001). There was a significant decrease (P < 0.05) in the proportion of patients taking a primary opioid on discharge 153 (58%) compared with admission 239 (83%), although the proportion of patients taking a strong opioid on discharge 150 (52%) compared with admission 135 (47%) was not significantly different (P > 0.05). The proportion of patients taking a laxative showed a significant increase on discharge 110 (73%) compared with admission 38 (28%) (P < 0.05). Conclusions Our analgesic prescribing scoring system and opioid conversion table have the potential to be developed further as tools for assessing opioid analgesic prescribing. The significant decrease in total daily oral morphine equivalents signifies the value of prescribing in accordance with the WHO analgesic ladder, and the necessity of general practitioner education. The management of chronic pain is complex, and it requires interventions additional to pharmacological therapy. Evaluation by a multidisciplinary team, coupled with experience in and an understanding of analgesic prescribing and rehabilitation provides an effective basis for improving the management of patients with chronic pain.
analgesic use, chronic pain, multidisciplinary pain centre, opioid analgesics, prescribing practices
Opioid analgesic prescribing and use - an audit of analgesic prescribing by general practitioners and The Multidisciplinary Pain Centre at Royal Brisbane Hospital
L M Nissen,1,2 S E Tett,1 T Cramond,2 B Williams,2 and M T Smith1