In many circumstances of data fitting one has to choose the optimal fitting function or model among several alternatives. Criteria or tests on which this decision is based are necessary and have to be well selected. In this preliminary analysis the application of the corrected Akaike information criterion is demonstrated considering the example of determining pharmacokinetic parameters for the blood serum time activity curves of 111In-labeled anti-CD66 antibody. Another model selection criterion, the F-test, is used for comparison. For the investigated data the corrected Akaike information criterion has proved to be an effective and efficient approach, applicable to nested and non-nested models.

This article reports the clinical investigation of a probe drug cocktail containing substrates of key drug transporters. Single oral doses of 0.25 mg digoxin (P‐gp), 5 mg furosemide (OAT1 and OAT3), 500 mg metformin (OCT2, MATE1, and MATE2‐K), and 10 mg rosuvastatin (OATP1B1, OATP1B3, and BCRP) were administered separately or as a cocktail in a randomized six‐period crossover trial in 24 healthy male volunteers. As a cocktail, relative bioavailabilities of digoxin and metformin and furosemide AUC0‐tz were similar to separate dosing. However, when administered as a cocktail the Cmax of furosemide was 19.1% lower and the Cmax and AUC0‐tz of rosuvastatin were 38.6% and 43.4% higher, respectively. In addition, the effects of increased doses of metformin or furosemide on the cocktail were investigated in 11 and 12 subjects, respectively. The cocktail explored in this trial has the potential to be used for the in vivo screening of transporter‐mediated drug–drug interactions. © 2016 American Society for Clinical Pharmacology and Therapeutics

OBJECTIVE To evaluate [11C]‐choline positron‐emission tomography (PET)/computed tomography (CT) for detecting clinical recurrence after primary treatment for prostate cancer. PATIENTS AND METHODS In all, 50 patients with prostate cancer who had had initial therapy (radical prostatectomy in 40, external beam radiation in three and interstitial brachytherapy in seven) had PET/CT using [11C]‐choline in the presence of an increased or increasing prostate‐specific antigen (PSA) level. The mean (range) time to biochemical progression was 22 (2–136) months. Current PSA levels were determined in all patients at the time of examination. The results were correlated with the histopathology reports after targeted biopsy or surgery, and with the clinical follow‐up. RESULTS The mean (median, range) PSA level in patients with positive PET/CT was 3.62 (2.42, 0.5–13.1) ng/mL, and that in patients with a negative scan was 0.90 (0.95, 0.41–1.40) ng/mL. PET/CT was positive in seven of 13 patients with a PSA level of <1.5 ng/mL, and histology was positive in this group in nine. In 17 patients with PSA levels of 1.5–2.5 ng/mL PET/CT was positive in all and the histology was positive in 13; in 11 men with a PSA level of 2.5–5 ng/mL PET/CT was positive in all 11 and the histology was positive in 10; in nine men with PSA levels of >5 ng/mL PET/CT identified all as positive and the histology was positive in eight. The sensitivity at a PSA level of <2.5 ng/mL of PET/CT for detecting recurrence was 91% (95% confidence interval, 71–99%) with a specificity of 50% (16–84)%. CONCLUSION [11C]‐choline PET/CT seems to be useful for re‐staging prostate cancer after curative therapy and with increasing PSA levels; this was verified by histological examination. We recommend this method at PSA levels of <2.5 ng/mL.

AimsPrevious pharmacokinetic characterization of a transporter probe cocktail containing digoxin (P‐gp), furosemide (OAT1, OAT3), metformin (OCT2, MATE1, MATE2‐K) and rosuvastatin (OATP1B1, OATP1B3, BCRP) in healthy subjects showed increases in rosuvastatin systemic exposure compared to rosuvastatin alone. In this trial, the doses of metformin and furosemide as putative perpetrators were reduced to eliminate their drug–drug interaction (DDI) with rosuvastatin.MethodsIn a randomized, open‐label, single‐centre, five‐treatment, five‐period crossover trial, 30 healthy male subjects received as reference treatments separately 0.25 mg digoxin, 1 mg furosemide, 10 mg metformin and 10 mg rosuvastatin, and as test treatment all four drugs administered together as a cocktail. Primary pharmacokinetic endpoints were AUC0‐tz (area under the plasma concentration–time curve from time zero to the last quantifiable concentration) and C max (maximum plasma concentration) of each probe drug.ResultsGeometric mean ratios and 90% confidence intervals of test (cocktail) to reference (single drug) for AUC0‐tz were 96.4% (88.2–105.3%) for digoxin, 102.6% (93.8–112.3%) for furosemide, 97.5% (93.5–101.6%) for metformin and 105.0% (96.4–114.4%) for rosuvastatin, indicating lack of interaction. The same analysis for C max and for pharmacokinetic parameters of urinary excretion of all cocktail components also indicated no DDI.ConclusionsDigoxin (0.25 mg), furosemide (1 mg), metformin (10 mg) and rosuvastatin (10 mg) exhibit no mutual pharmacokinetic interactions and are well tolerated administered as a cocktail. The cocktail is thus optimized and has the potential to be used as a screening tool for clinical investigation of transporter‐mediated DDI.

[(11)C]choline PET/CT is useful for re-staging of prostate cancer in patients with rising PSA even at levels below 1.5 ng/ml. Our study confirms results from other published studies on [(11)C]choline PET/CT in prostate cancer relapse.