AIMTo investigate the in vitro recovery and influencing factors of ketoprofen in microdialysis probe, and study the pharmacokinetic of unbound ketoprofen in rat after iv administration.

METHODSThe recovery of ketoprofen was detected by a concentration difference method. After microdialysis probe was inserted into the jugular vein of male Wistar rats, the probe was infused with various concentrations perfusate. The in vivo recovery and the pharmacokinetics of unbound ketoprofen in rat were investigated. Dialysate samples were determined by HPLC.

RESULTSThe recovery detected by gain was as the same as that by loss; the recovery was independent of the drug concentration surrounding the probe. The in vitro recovery was 28.75% by concentration difference method and the in vivo recovery was (40.3 +/- 2.7) % by retrodialysis method. After i.v. administration of ketoprofen in rat, T 1/2, AUC and CL of unbound ketoprofen were (181 +/- 16) min, (112 +/- 27) microg x min x mL(-1) and (0.22 +/- 0.05) L x min(-1), respectively.

CONCLUSIONMicrodialysis sampling can be used for the pharmacokinetic study of unbound ketoprofen in rat.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; pharmacokinetics ; Area Under Curve ; Chromatography, High Pressure Liquid ; Injections, Intravenous ; Ketoprofen ; administration & dosage ; pharmacokinetics ; Male ; Microdialysis ; methods ; Rats ; Rats, Wistar

OBJECTIVETo evaluate the clinical efficacy and safety of dexketoprofen trometamol in the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

METHODSA total of 115 patients with CP/CPPS were divided into a dexketoprofen trometamol group (n = 40), treated with dexketoprofen trometamol (25 mg, tid) and terazosin (2 mg, qn), an indometacin group (n = 40) given indometacin (25 mg, tid) and terazosin (2 mg, qn), and a terazosin group (n = 35) administered terazosin (2 mg, qn) only, all treated for 4 weeks. Scores on the NIH-chronic prostatitis symptom index (NIH-CPSI) were obtained before and after the treatment, and the efficacy and adverse events were observed and compared.

RESULTSThe NIH-CPSI scores were significantly improved after the treatment in all the three groups. The clinical efficacy was significantly better in the dexketoprofen trometamol and indometacin groups than in the terazosin group (P < 0.05), but with no significant difference between the former two (P > 0.05). The rates of adverse events were 10.00%, 18.57% and 27.50% in the dexketoprofen trometamol, terazosin and indometacin groups, significantly lower in the former two than in the latter one (P < 0.05).

CONCLUSIONThe combination of dexketoprofen trometamol with terazosin could effectively improve the clinical symptoms of CP/CPPS, better than terazosin in therapeutic efficacy and than indometacin in drug tolerance.

Adult ; Chronic Disease ; Humans ; Indomethacin ; administration & dosage ; therapeutic use ; Ketoprofen ; administration & dosage ; analogs & derivatives ; therapeutic use ; Male ; Pelvic Pain ; drug therapy ; Prazosin ; administration & dosage ; analogs & derivatives ; therapeutic use ; Prostatitis ; drug therapy ; Tromethamine ; administration & dosage ; analogs & derivatives ; therapeutic use

AIMTo establish an in situ perfused pig ear model for percutaneous absorption.

METHODSThe in situ perfused pig ear model for percutaneous absorption consisted of artificial gas, sample chamber, constant flow pump, constant temperature system, polytetrafluorethylene connective tube, porcine ear vein, porcine ear skin and special laminar flow apparatus. The perfused system viability was assessed by glucose utilization and lactate production. Ketoprofen isopropyl ester and methyl salicylate was used for validating this model. The concentrations of perfused sample were measured by HPLC.

RESULTSGlucose utilization and lactate production showed that this model was viable till 7 h. Ketoprofen isopropyl ester was completely metabolized to ketoprofen in situ in perfused pig ear model. The steady cumulative amount (Q) of ketoprofen from permeation and metabolism was linear with time (t), the equation of ketoprofen formation was Q = -0.024 + 0.120t, the rate of ketoprofen formation was 0.120 microgram.cm-2.h-1. Methyl salicylate was partially metabolized to salicylic acid. The steady cumulative amount (Q) of methyl salicylate from permeation was linear with time (t), the permeation equation of methyl salicylate was Q = -3.809 + 6.129t, the permeation rate of metyl salicylate was 6.129 micrograms.cm-2.h-1. The steady cumulative amount (Q) of salicylic acid from metabolism was also linear with time (t), the formation equation of salicylic acid was Q = -1.785 + 0.879t, the formation rate of salicylic acid was 0.879 microgram.cm-2.h-1.

CONCLUSIONThe in situ pig ear vein perfused model is a novel easy-handing and cost-efficient technique for percutaneous absorption and skin metabolism.

Administration, Cutaneous ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; metabolism ; pharmacokinetics ; Ear, External ; blood supply ; Ketoprofen ; administration & dosage ; metabolism ; pharmacokinetics ; Male ; Models, Animal ; Perfusion ; Salicylates ; administration & dosage ; pharmacokinetics ; Salicylic Acid ; metabolism ; Skin ; metabolism ; Skin Absorption ; Swine ; Veins

This study demonstrates that prophylactic effect of plaster and cataplasm contained ketoprofen in adjuvant arthritis therapy by X-ray. Adjuvant arthritis was induced by a single injection of Freund's complete adjuvant. Mature female Sprague-Dawley rats were designated to 3 groups such as nontreated control, plaster-treated (PT) and cataplasm-treated (CT), each of which was composed of ten animals. The PT and the CT groups showed reduced primary paw swelling, but secondary paw swelling was not affected. Bony changes were observed in all regions of the femur and tibia of the nonadjuvant-injected leg and the adjuvant-injected leg. The mean radiographic scores of the PT and the CT groups were significantly lower than those of the control group from day 0 to 7 of the experimental period (p<0.05, p<0.01). The CT rats showed reduced poly-arthritis development than the PT rats. Our results suggest that radiographic assessment of bony changes is more suitable for measuring changes in long bones such as femur or tibia than in vertebrae. The prophylactic effect of CT prominently suppressed edematous swelling and bony changes in arthritic limb compared with PT.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*pharmacology ; Arthritis, Experimental/*prevention & control ; Calcium Sulfate ; Drug Carriers/administration & dosage ; Excipients/*administration & dosage ; Female ; Freund's Adjuvant ; Ketoprofen/*administration & dosage/analogs & derivatives/therapeutic use ; Rats ; Rats, Sprague-Dawley

AIMTo reconstruct of a tissue engineering skin in vitro for the study of the use of drug percutaneous penetration and metabolism.

METHODSDermal fibroblasts were embedded in collagen type I. HaCaT cells were seeded on the top of the gel. The skin was generated through air-liquid interface culture. Effects of various culture media on tissues morphology were investigated. Sections of the cultured skin were stained with hematoxylin and eosin and examined under microscope. Permeation and metabolism of ketoprofen and its isopropyl ester through the cultured skin were investigated.

RESULTSHaCaT cells initially developed a multilayer epithelium at the air-liquid interface, but it showed a parakeratotic stratum corneum. Vitamin C enhanced cell proliferation obviously. Vitamin D3 promoted cell differentiation. And estradiol showed little effect on the tissue engineering skin. Ketoprofen isopropyl ester was hydrolyzed into ketoprofen when penetrated through the cultured skin, which resembled in the skin cell homogenates metabolism.

CONCLUSIONCultured at the air-liquid interface, HaCaT cells developed a parakeratotic mutilayer epithelium. Enzyme activity was reserved. This cultured skin could serve as an appropriate model for drug percutaneous metabolism and skin irritation.

Administration, Cutaneous ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacokinetics ; Esters ; administration & dosage ; chemistry ; pharmacokinetics ; HeLa Cells ; cytology ; Humans ; Ketoprofen ; administration & dosage ; chemistry ; pharmacokinetics ; Skin Absorption ; Skin, Artificial ; Tissue Engineering ; methods