Preparation and Pharmacological Evaluation of Novel Orally Active Ester Prodrugs of Ketoprofen with Non-Ulcerogenic Property

• Published in: Chemical biology & drug design Vol. 87; no. 6; pp. 878 - 884
• Main Authors: Dhakane, Valmik D., Thakare, Vishnu N., Dongare, Sakharam B., Bhale, Pravin S., Mule, Yoginath B., Bandgar, Babasaheb P., Chavan, Hemant V.
• Format: Journal Article
• Language: English
• Published: HOBOKEN Blackwell Publishing Ltd 01.06.2016; Wiley
• Subjects: Administration, Oral; Animals; anti-inflammatory activity; Biochemistry & Molecular Biology; Chemistry, Medicinal; Drug Evaluation, Preclinical; ketoprofen; Ketoprofen - adverse effects; Ketoprofen - chemical synthesis; Ketoprofen - chemistry; Ketoprofen - pharmacokinetics; Life Sciences & Biomedicine; Mice; non-ulcerogenic; pharmacokinetic profile; Pharmacology & Pharmacy; prodrug; Prodrugs - adverse effects; Prodrugs - chemical synthesis; Prodrugs - chemistry; Prodrugs - pharmacokinetics; Rats; Science & Technology; Sigmodontinae; Stomach Ulcer - blood; Stomach Ulcer - chemically induced; ketoprofen; prodrug; pharmacokinetic profile; RAT; non-ulcerogenic; PAW; CARRAGEENIN; anti-inflammatory activity
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.12719

This study investigates anti‐inflammatory activity with improved pharmacokinetic and non‐ulcerogenic properties of various novel synthesized prodrugs of ketoprofen in experimental animals. Prodrugs 3a, 3f and 3k were found to possess significant anti‐inflammatory activity with almost non‐ulcerogenic potential than standard drug ketoprofen (1) in both normal and inflammation‐induced rats. The experimental findings elicited higher AUC and plasma concentration at 1 and 2 h indicating improved oral bioavailability as compared to parent drug ketoprofen. These prodrugs are found to have no gastric ulceration with retained anti‐inflammatory activity. Therefore, present experimental findings demonstrated significant improvement of various pharmacokinetic properties with non‐ulcerogenic potential of ester prodrugs of ketoprofen. A series of ester prodrugs of ketoprofen were synthesized and evaluated as novel anti‐inflammatory agents. Prodrugs 3a, 3f, and 3k were found to possess significant anti‐inflammatory activity with almost non‐ulcerogenic potential than ketoprofen (1).