ABSTRACT
Curcumin, a lipophilic polyphenol derived from the roots of Curcuma longa. Recently, it has been widely investigatedas a therapeutic agent for cancer. Thus, there is a growing interest in measuring curcumin concentrations in theplasma and other target tissues in relevant animal models. We developed and validated a simple, fast, and reliablemethod for quantifying curcumin in biological matrices by Ultra Performance Liquid Chromatography (UPLC)-MassSpectrometry (MS)/MS. The liquid chromatography system is using rapid separation on Acquity UPLC®BEH C18with gradient mobile phase contained formic acid and acetonitrile. Prior to detection, curcumin and internal standard(IS) were ionized using electrospray ionization positive source and the ions were monitored at m/z 369 → 177 and 260→ 183 for curcumin and IS, respectively. The calibration curve was linear (r ≥ 0.99) over the concentration range of1–50 ng/ml and 1–30 ng/ml for rat plasma and for ovary homogenate, respectively. The lower limit of quantificationwas 1 ng/ml. The mean accuracy ranged from 98.9% to 103.2% and 98% to 108.9%, while the coefficient of variation(CV) values of precision in rat plasma were below 11.92% and 10.47% for within and between run, respectively. Inrat ovary homogenate, the mean concentration and CV of within run accuracy and precision were 95.53%–109.78%and 3.34%–9.14%, respectively. The developed method was used to quantify curcumin in rat plasma and ovary afteran oral gavage. In conclusion, the developed and validated method should be useful for quantification of curcuminaccurately and precisely in plasma and target organs from relevant animal models of human diseases.
ABSTRACT
Background: The present study was aimed to explore the effects of ritonavir and primaquine combination given as a singledose or repeated-dose compared to ritonavir alone on ritonavir plasma concentration in the rats. Methods: In single-dose study, 30 male Spraque Dawley rats were randomly allocated to receive ritonavir 20 mg/kg BW or ritonavir 20 mg/kg BW + primaquine 1.2 mg/kg BW or ritonavir 20 mg/kg BW + ketokonazole 10 mg/kg BW. Ketokonazole was used as positive control of ritonavir metabolism inhibitor. In the repeated-dose study, thirty Spraque Dawley male rats were randomly allocated to receive ritonavir 20 mg/kg BW/day or ritonavir 20 mg/kg BW/day + primaquine 1.2 mg/kg BW/day or ritonavir 20 mg/kg BW/day + rifampicin 100 mg/kg BW/day. Rifampicin was used as a positive control of ritonavir metabolism inducer. Results: In the single-dose study, ketokonazole increased the area under the plasma concentration (AUC) of ritonavir (↑114.8%, p< 0.05), while primaquine tended to decrease the AUC of ritonavir (↓ 32.6%, p> 0.05). Repeated-dose study showed that rifampicin decreases the AUC of ritonavir (↓ 42.8%, p< 0.001), and primaquine decreased the AUC of ritonavir plasma concentration (↓ 46.6%, p< 0.001). Conclusion: Concomitant administration of primaquine and ritonavir decreases the AUC of ritonavir. This effect may result in the insufficient concentration of ritonavir as anti-HIV, which may lead to treatment failure with ritonavir.
Subject(s)
Rats, Sprague-Dawley , Ritonavir , PrimaquineABSTRACT
Aim Dose adjusment and drug selection is important in patient with renal dysfuction.This study was aimed to assess the accuracy of dose adjustment and drug selection for renal dysfunction patient at the Internal Medicine Ward FMUI/Dr. Cipto Mangunkusumo Hospital, Jakarta Methods Patients ≥ 18 years old with estimated creatinine clearance < 60 mL/minute based on Cockroft-Gault formula were included in this study. The drugs assessed were those excreted by the kidney or having nephrotoxic effect. The appropriateness of drug selection is assessed based on the preserce or not contraindication or potential of drug-drug interaction. The accuracy of dose adjustment were assessed based on information available in various textbooks, literatures, and drug brochures. Data were collected between May to July 2007. Results Data obtained from 43 patients met the inclusion criterias demonstrated that 164 out of 385 drug prescriptions were mainly eliminated by the kidney or have nephrotoxic characteristic. Out of 164 drug prescriptions, 142 (86.5%) were appropriately adjusted, while the other 22 (13.5%) were inappropriately adjusted for the dose. There was only one contraindication for the usage of the drug and 15.1% potentially drug interaction. Conclusion Dose adjustment and drug selections in patients with renal dysfunction at the Internal Medicine Ward FMUI/Dr. Cipto Mangunkusumo Hospital are conducted appropriately.