2002
DOI: 10.1007/bf03190426
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Drug interaction studies between paclitaxel (Taxol) and OC144-093 — A new modulator of MDR in cancer chemotherapy

Abstract: The MDR modulator, OC144-093, is a potential candidate for use in cancer therapy and exhibits potent biological activity in vitro and in vivo when combined with anticancer agents such as paclitaxel. Its inhibitory interaction with P-glycoprotein (Pgp), the mdr1 gene product and a mechanistic participant in multidrug resistance, underlies its activity as a modulator of MDR. Having previously shown that OC144-093 is not a substrate for CYP3A we first examined the effects of OC144-093 on paclitaxel metabolism in … Show more

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Cited by 32 publications
(16 citation statements)
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“…Some of the higher profile examples include: i) the cyclosporin A derivative valspodar (PSC-833); 6 ii) Vertex Pharmaceutical's biricodar (VX-710); 7 iii) the anthranilamide-based modulators XR9051 ( 2 ), 8 tariquidar (XR9576), 9-10 XR9577, 11 and WK-X-34; 11 iv) acridone carboxamide derivative elacridar (GF120918); 12 v) the heteroaryloxypropanolamines zosuquidar (LY335979), 13 dofequidar (MS-209) 14 and laniquidar; 15 and vi) the diarylimidazole ontogen (OC144-093, ONT-093). 16 The later generation inhibitors tended to be more potent and less toxic than the first generation compounds; however, multiple off-target issues remain.…”
Section: Introductionmentioning
confidence: 99%
“…Some of the higher profile examples include: i) the cyclosporin A derivative valspodar (PSC-833); 6 ii) Vertex Pharmaceutical's biricodar (VX-710); 7 iii) the anthranilamide-based modulators XR9051 ( 2 ), 8 tariquidar (XR9576), 9-10 XR9577, 11 and WK-X-34; 11 iv) acridone carboxamide derivative elacridar (GF120918); 12 v) the heteroaryloxypropanolamines zosuquidar (LY335979), 13 dofequidar (MS-209) 14 and laniquidar; 15 and vi) the diarylimidazole ontogen (OC144-093, ONT-093). 16 The later generation inhibitors tended to be more potent and less toxic than the first generation compounds; however, multiple off-target issues remain.…”
Section: Introductionmentioning
confidence: 99%
“…38 L/h for Case 2) when CL was not less than the standard. If CL is less than the standard, the CL fold change was defined as the negative ratio of the standard CL (38 L/h for Case 2) to the CL used in the simulation (CL sim ) as shown in equation (4 b n1, n2, ..., n10, n11 have the similar meaning as in footnote a except that they represent 11 numbers from 1 to 5 considering the bioavailability limit (0 to 1).…”
Section: Glossarymentioning
confidence: 99%
“…[2,3] The second category includes the cases in which AUC has larger fold changes compared to C max . [4][5][6][7][8] In cases of the third category, C max has larger fold changes compared with AUC. [9][10][11][12][13][14][15][16][17][18] It is interesting to note that rosuvastatin in three different studies with three different concomitant medications (gemfibrozil, [6] lopinavir/ ritonavir [7] and ciclosporin, [8] respectively) showed similar pattern with C max having higher fold changes compared to AUC fold changes, although the absolute fold changes were different (2.21, 4.7 and 10.6 for C max , respectively).…”
Section: Introductionmentioning
confidence: 99%
“…[2,3] The second category includes the cases in which AUC has larger fold changes compared to C max . [48] In cases of the third category, C max has larger fold changes compared with AUC. [9–18]…”
Section: Introductionmentioning
confidence: 99%