Pharmacokinetics of indomethacin

Alván, Gunnar; Orme, M.; Bertilsson, Leif; Ekstrand, Roger; Palmér, Lena

doi:10.1002/cpt1975183364

Cited by 231 publications

(101 citation statements)

References 9 publications

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“…The choice of indomethacin, administered rectally, was made on the basis of its well studied physiological properties, good absorption, easy and convenient (q12h) administration, and relative inexpensiveness. 13 The standard postoperative analgesia technique used in many institutions for cardiac surgery does not involve the use of NSAIDs. Through a prospective, randomized, double-blind trial, comparing indomethacin with placebo, as an adjunct to morphine analgesia, we recorded the effects of indomethacin on morphine use and analgesia after cardiac surgery.…”

mentioning

confidence: 99%

Rectal indomethacin reduces postoperative pain and morphine use after cardiac surgery

Rapanos

Murphy

Szalai

et al. 1999

Can J Anesth/J Can Anesth

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Rectal indomethacin reduces postoperative pain and morphine use after cardiac surgeryPurpose: To evaluate the combination of rectal indomethacin with patient controlled intravenous morphine analgesia (PCA) on postoperative pain relief and opioid use after cardiac surgery. Methods: With institutional ethics approval, 57 consenting adults undergoing elective aortocoronary bypass surgery were randomly assigned preoperatively in a double-blind fashion to receive either placebo in = 26) or indomethacin 100 mg suppositories (n = 31 ), 2-3 hr postoperatively, and 12 hr later. Both groups utilized PCA morphine. Pain scores in the two treatment groups were assessed on a 10-cm visual analogue scale (VAS) (at rest and with cough) at 4, 6, 12, 18 and 24 hr after initial dosing, and were analyzed through a 2 x 5 repeated measures of variance. The 24 hr analgesic consumption, 12 and 24 hr chest tube blood loss, and time to tracheal extubation were also recorded, and compared for the two treatment arms through Student's t test on independent samples. Results: Postoperative morphine consumption in the first 24 hr was 38% less in the indomethacin group (22.40 _+ 12.55 mg) than the placebo group (35.99 +_ 25.84 mg), P= 0.019. Pain scores, measured with a VAS, were 26% to 66% lower in the indomethacin vs placebo group at rest (P=0.006), but not with cough, for all times assessed. There was no difference in blood loss (at 12 hr) or time to tracheal extubation for both groups.

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confidence: 99%

Rectal indomethacin reduces postoperative pain and morphine use after cardiac surgery

Rapanos

Murphy

Szalai

et al. 1999

Can J Anesth/J Can Anesth

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“…We compared the inhibitory effect of indomethacin on tumor growth with the reported inhibitory effects of other chemotherapeutic agents: the maximal reduction of 55% in Colon-26 tumor size of our study is comparable with the antitumor effect of cisplatin, 17) as well as the antitumor effect of 5-fluorouracil alone in Meth-A tumor-bearing mice, 18) and the maximal tumor size reduction of 40% in the FM3A tumor in our study is comparable with the antitumor effect of bleomycin 19) or UFT (a fluorouracil compound) 20) alone. However, in our in vitro study, the concentration equivalent to the achievable maximal plasma concentration (MPC), which is a little higher than 1.0 µg/ml, 21) did not show a cytotoxic effect on Colon 26, Meth-A and FM3A tumor cells, as judged from the IC 50 values of indomethacin in these tumor cells using MTT assay. The IC 50 values of indomethacin in the three types of tumor cells were about 100-fold higher than the MPC in vivo.…”

Section: Discussionmentioning

confidence: 56%

Indomethacin Suppresses the Growth of Colon 26, Meth‐A and FM3A Tumors in Mice by Reducing the Prostaglandin E₂ Content and Telomerase Activity in Tumor Tissues

Ogino

Higuchi

Murata³

et al. 1999

Japanese Journal of Cancer Research

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The antitumor effect of indomethacin on Colon 26, Meth-A and FM3A tumors was investigated in mice. The prostaglandin E 2 content in tumor tissues was assayed to find out if indomethacin acts on tumors, and the telomerase activity in tumors and somatic tissues (testis, liver, spleen and colon) was also monitored during indomethacin treatment. Growth of Colon 26, Meth-A and FM3A tumors was significantly (P< < < <0.001-0.05) suppressed by indomethacin compared to the untreated controls. The prostaglandin E 2 content in the three tumors was markedly (P< < < <0.001) reduced by indomethacin. Telomerase activity in Colon 26 and FM3A tumors was significantly (P< < < <0.001) lower than that of untreated tumors (80% and 45% decrease versus the controls, respectively), and the activity in Meth-A tumor was slightly decreased (10% decrease versus the control) by indomethacin. Telomerase activity in the somatic tissues was not significantly affected by indomethacin. In summary, this study shows the effectiveness of indomethacin as an antitumor agent against three types of tumors, and suggests that indomethacin affects telomerase activity in tumors in vivo.Key words: Indomethacin -Prostaglandin E 2 -Telomerase activity -Fluorescence-based telomeric repeat amplification protocolThe antitumor effect of indomethacin on tumors in cancer patients 1, 2) and in animals 3, 4) has been described. We previously showed that indomethacin suppresses the growth of Colon 26 tumor in mice by enhancing the cellular immune function and improving cancer cachexia. 5)Indomethacin does not have a cytotoxic effect on Colon 26 tumor cells in vitro, 5) but it may have an antitumor effect via immunological pathways. We previously reported that indomethacin treatment of tumors reduces tumor size less in nude mice (deficient in T-lymphocytes) than in normal mice, compared with untreated tumors. 6)Although these results indicate that the effectiveness of indomethacin as an antitumor agent is, at least in part, due to its modification of T-cell-mediated immune functions, the precise mechanism of tumor growth suppression by indomethacin remains unknown.Recent studies have shown that many proliferating tumor cells retain a certain level of telomerase activity. [7][8][9] We previously reported that tumor growth in Colon 26-bearing mice is significantly suppressed by indomethacin treatment compared with the untreated controls, and that the telomerase activity declines preferentially in tumor tissues, while telomerase activity in somatic tissues is not significantly affected by indomethacin treatment.10) More recently, Kido et al. 11) reported that tumor size reduction by cisplatin treatment correlates with a decline in telomerase activity in tumor tissues.In this study, we transplanted Colon 26, Meth-A and FM3A tumors into normal mice to assess if the effect of indomethacin is independent of tumor cell type. Prostaglandin E 2 synthesis is inhibited by indomethacin, and therefore we measured the prostaglandin E 2 content in tumors to confirm the effect of ind...

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“…mean) (Alvan et al, 1975;Baber et al, 1979). In humans, indoprofen is absorbed rapidly following oral administration.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetic profile of indoprofen in elderly subjects.

Lund¹,

Egsmose²,

Knudsen³

et al. 1986

Brit J Clinical Pharma

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Pharmacokinetics of indomethacin

Cited by 231 publications

References 9 publications

Rectal indomethacin reduces postoperative pain and morphine use after cardiac surgery

Rectal indomethacin reduces postoperative pain and morphine use after cardiac surgery

Indomethacin Suppresses the Growth of Colon 26, Meth‐A and FM3A Tumors in Mice by Reducing the Prostaglandin E₂ Content and Telomerase Activity in Tumor Tissues

Pharmacokinetic profile of indoprofen in elderly subjects.

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Pharmacokinetics of indomethacin

Cited by 231 publications

References 9 publications

Rectal indomethacin reduces postoperative pain and morphine use after cardiac surgery

Rectal indomethacin reduces postoperative pain and morphine use after cardiac surgery

Indomethacin Suppresses the Growth of Colon 26, Meth‐A and FM3A Tumors in Mice by Reducing the Prostaglandin E2 Content and Telomerase Activity in Tumor Tissues

Pharmacokinetic profile of indoprofen in elderly subjects.

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Indomethacin Suppresses the Growth of Colon 26, Meth‐A and FM3A Tumors in Mice by Reducing the Prostaglandin E₂ Content and Telomerase Activity in Tumor Tissues