재발성 또는 지속성 상피성 난소암에서의 Docetaxel 요법의 효용성 및 독성

주다혜 ( Da Hye Ju ),김용만 ( Yong Man Kim ),김민균 ( Min Gyun Kim ),김유진 ( Eu Gene Kim ),김대연 ( Dae Yeon Kim ),서대식 ( Dae Sik Seo ),김종혁 ( Jong Hyeok Kim ),김영탁 ( Young Tak Kim ),남주현 ( Joo Hyun Nam ) 대한산부인과학회 2007 Obstetrics & Gynecology Science Vol.50 No.11

목적: Paclitaxle-platinum 병합요법 치료 후, 재발하거나 반응이 없는 상피성 난소암에서 docetaxel 단독 및 병합 요법의 치료에 대한 효과 및 독성을 알아보고자 하였다. 연구 방법: 1989년 5월부터 2006년 12월까지 서울아산병원에서 재발성 혹은 지속성 상피성 난소암 환자 중 docetaxel 단독 요법 및 다른 항암제와의 병합 요법을 받은 40명의 환자를 대상으로 하였다. Docetaxel 요법은 docetaxel 75 mg/m2 단독 요법이나 docetaxel과 platinum (carboplatin AUC5 또는 cisplatin 75 mg/m2)을 1 일째 투여하는 병합 요법으로 하여 3~4주 간격으로 시행하였다. 치료 효과는 RECIST criteria와 CA-125 response criteria 정의에 따라 평가하였다. 약제 독성은 NCI Common Toxicity Criteria에 따라 평가하였다. 결과: 20명은 RECIST criteria를 기준으로, 20명은 CA-125 response criteria의 정의에 따라 평가하였다. 전체 반응률은 35% (14/40)이었고, 완전 반응은 11명 (27.5%)이었으며, 부분 반응은 3명 (7.5%)이었다. 40명의 재발성 난소암의 환자들의 평균 치료 반응 기간은 11.29개월 (4~20.7개월), 평균 병의 진행 기간은 6.91개월 (1~23개월)이었다. Platinum sensitivity에서 반응군에서는 38.7%, 저항군에서는 22.2%의 반응률을 보여 통계적으로 유의하지 않았으나 (p=0.776) 반응군에서 더 높은 반응률을 보였다. 한편 이전 3회 이상의 치료를 받은 군에서 그렇지 않은 군보다 통계적으로 유의하게 낮은 반응률을 보였다 (p=0.022). 가장 흔한 약제 독성은 탈모와 위장관계 독성이었으며, 가장 심각한 약제 독성은 골수 억제 반응이었다. 결론: 초회 치료로 paclitaxel-platinum 병용 요법을 사용 한 재발성 또는 지속성 상피성 난소암 환자에서 docetaxel은 효과와 독성 면에서 2차 치료약제로 고려할 만한 약제이다. Objective: The aim of this study is to determine the efficacy and toxicity of docetaxel in patients with recurrent or persistent epithelial ovarian cancer, previously treated with paclitaxel and platinum combination chemotherapy. Methods: Forty patients with recurrent or persistent epithelial ovarian cancer, had been treated with docetaxel combination chemotherapy at Asan Medical Center from May 1989 to December 2006. They received docetaxel (75 mg/m2) only or docetaxel (75 mg/m2) and platinum (carboplatin AUC5 or cisplatin 75 mg/m2) on day 1. The administration was repeated every 3 or 4 weeks. The response of patients was evaluated with CA-125 response criteria and RECIST criteria. The toxicities were defined according to the NCI common toxicity criteria. Results: Twenty patients had been evaluated by RECIST criteria and twenty patients had been evaluated by CA-125 response criteria. The overall response rate was 35% (14/40). Eleven patients were belonged to complete response (CR), and three patients were belonged to partial response (PR). The mean response duration (RD) was 11.29 months (4 to 20.7 months) and the mean time to progression (TTP) was 6.91 months (1 to 23 months). The response rate in the platinum-sensitive patients was 38.7% but in the platinum-resistant patients was 22.2%. The platinum-sensitive patients showed more favorable response rate, but that was not significant statistically. Heavily treated group, more than three prior regimens were used, had poor outcome. The common toxicities were alopecia and gastrointestinal toxicities (anorexia and nausea). Bone marrow suppression was the most serious drug toxicity, however, it was tolerable. Conclusion: The docetaxel is a considerable 2nd line chemotherapy with acceptable efficacy and toxicity in patients with recurrent or persistent epithelial ovarian cancer previously treated with paclitaxel and platinum combination chemotherapy.

진행성 비소세포폐암 환자에서 제1차 요법으로서 매주요법 Docetaxel/Platinum 복합항암화학요법의 효과

김소연 ( So Yeon Kim ),류헌모 ( Hun Mo Ryoo ),배성화 ( Sung Hwa Bae ),정현영 ( Hyun Young Jung ),김경찬 ( Kyung Chan Kim ),현대성 ( Dae Sung Hyun ),이상채 ( Sang Chae Lee ),김경옥 ( Kyeong Ok Kim ),이경희 ( Kyung Hee Lee ),현명수 대한내과학회 2007 대한내과학회지 Vol.72 No.6

목적: 비소세포폐암은 최근 지속적으로 증가하며 대다수의 환자가 질병 경과 중에 항암화학요법이 필요하다. Docetaxel과 platinum의 복합항암화학요법이 비소세포폐암의 치료에 효과적이지만 표준적인 3주요법은 심각한 골수 억제 독성이 있다. 주 단위 저용량의 docetaxel을 투여할 경우 효과를 유지하면서 골수 억제 독성을 감소시킨다고 한다. 이에 저자들은 진행성 비소세포폐암 환자에서 주 단위 저용량 docetaxel과 platinum 복합항암화학요법의 효과와 독성을 알아보기 위해 본 연구를 시행하였다. 방법: 2004년 7월부터 2005년 12월까지 총 29명의 완치가 불가능한 비소세포폐암 환자를 대상으로 docetaxel 35 mg/m2를 제 1, 8, 15일에 1시간 동안 정맥점적주사하고, 제1일에 cisplatin 75 mg/m2 (60세 미만) 또는 carboplatin (AUC 6, 60세 이상)을 docetaxel 투여 후 정맥점적주사하였다. 결과: 총 29명 중 남자 25명, 여자 4명이었고, 중앙 연령 66세, 60세 이상 65.5%, 일상생활수행능력(ECOG) 2가 55.2%였다. 편평상피세포암 48%, 선암 38%였다. 제IIIB병기 21%, 제IV병기 72%, 수술 후 재발한 환자 7%였다. 복합항암화학요법은 총 95회를 투여하였다. 평가 가능한 26명에서 부분반응 44.8%, 안정성 병변 10.3%, 진행성 병변 34.5%로 전체종양반응률 44.8%였다. 중앙 생존기간 11.3개월(95% 신뢰구간, 23-67주), 무진행생존기간 5.3개월(95% 신뢰구간, 11-31주), 1년 추정 생존률 37%였다. 연령, 성별, 병기, 일상생활수행능력 및 조직학적 아형에 따른 생존률은 통계학적으로 의미있는 차이는 없었다. 결론: 진행성 비소세포폐암 환자에서 저용량의 docetaxel 매주요법과 platinum 제제의 복합항암화학요법은 3주요법과 대등한 전체 종양 반응률과 중앙생존기간을 보이면서 낮은 혈액학적 독성을 보여 일상생활수행능력이 불량하거나 고령인 환자를 포함하여 비소세포폐암의 새로운 치료법이 될 수 있을 것으로 생각한다. Background: Docetaxel is a highly effective chemotherapeutic agent with proven efficacy for non-small cell lung cancer (NSCLC). However, myelosuppression can be a substantial concern when docetaxel is administered every 3 weeks. Weekly administration of low-dose docetaxel has demonstrated a comparable efficacy together with a distinct toxicity profile with reduced myelosuppression. We conducted a phase Ⅱ study of weekly administration of docetaxel and cisplatin or carboplatin in patients with advanced NSCLC to evaluate efficacy and safety. Methods: Twenty-nine patients with advanced or metastatic NSCLC who had not received prior treatment were enrolled in the study. The patients received intravenous infusions of docetaxel (35 mg/m2 on days 1, 8, 15) and cisplatin (75 mg/m2 on day 1) or carboplatin (AUC 6), followed by a week of rest. Results: Twenty-six patients were assessable for efficacy and all patients were assessable for toxicity determination. The overall response rate of the regimen was 44.8%. The median survival was 11.3 months, and the 1-year survival rate was 37%. Of the hematologic toxicities, grade 3/4 neutropenia were observed in 12.6% of the patients, but there were no episodes of neutropenic fever. Non-hematologic toxicities were mild. Conclusions: With this weekly dosing regimen, although efficacy is comparable, myelosuppression is substantially less, and the overall tolerability profile is better than with dosing every 3 weeks. (Korean J Med 72:625-631, 2007)

진행성 비소세포폐암의 이차항암화학요법으로서 Docetaxel 단독요법의 성적

강현모,이정은,장필순,이연선,권선중,안진영,정성수,김주옥,김선영 충남대학교 암공동연구소 2006 암공동연구소 업적집 Vol.5 No.

Background : The survival benefit associated with first-line chemotherapy in lung cancer has led to the need for second -line chemotherapy, for which Docetaxel (Taxotere^(?)) has proven efficacy in both settings. This study evaluated the safety and efficacy of docetaxel in patients with non-small cell lung cancer who had failed first-line platinum-based chemotherapy. Methods : Thirty one patients with non-small-cell lung cancer, who had failed first line platinum-based chemotherapy, between March 1999 and August 2003, were enrolled in this study. Patients received intravenous docetaxel, either 75 mg/㎡ or 100 mg/㎡, with routine premedication every three weeks. Results : Fourteen patients (45.2%) had a partial response. The median survival and progression- free survival times were 12.5 months (95% CI 7.3-17.6) and 3.0 months (95% CI 1.6-4.5), respectively. This study showed 2 factors gave different survival benefits; the age (< 60 years: 20.1 months vs. > 60 years: 6.6 months, p=0.0105) and the histological type (adenocarcinoma: 25.6 months vs. others: 7.9 months, p=0.0055). The predominant toxicity was neutropenia, which occurred as WHO grade 3 or 4 in 38.7 % of patients. One treatment related death was also reported. Non-hematological toxicity was minor and easily controlled. There were no significant statistical differences in the survival benefit and toxicity between the two doses. Conclusion : Docetaxel, as second-line monotherapy, was well tolerated and effective in patients with non-small-cell lung cancer who failed first line platinum -based chemotherapy. (Tuberc Respir DiS 2005: 58: 465-472) 연구배경 : 일차항암화학요법 후에 생존의 이득을 얻었음에도 불구하고 비소세포폐암 환자들의 대다수가 결국은 재발하거나 진행성 병변을 보인다. 이에 저자들은 기존의 여러 연구에서 보고 된 구제요법으로서 docetaxel의 항암효과와 비교적 적은 독성의 결과를 바탕으로,platinum을 근거로 한 항암화학요법을 시행 밖았으나 개발되거나 진행된 비소세포폐암 환자들을 대상으로 docetaxel 단독요법의 치료효과와 부작용에 대하여 알아보고자 하였다. 방법 : 조직학적으로 비소세포폐암으로 진단을 받고 platinum을 근거로 한 항암화학요법을 받았으나 재발 또는 진행성 병변을 보인 31명의 환자들을 대상으로 docetaxel 75 mg/m² 또는 100 mg/m²을 3주마다 정주하였다. 임상기록을 통한 후향적인 방법으로 분석하였다. 결과 : 1) 재발 또는 진행성 병변을 보인 31명중 남녀 비는 24:7이고 중앙연령은 60세였다. 2) 반응평가로 완전 관해는 없었고 부분관해는 14명(45.2%), 불변이 10명(32.3%), 진행이 7명(22.6%)으로 전체적인 반응율은 45.2%이었다. 3)중앙생존기간은 12.5개월(95% 신뢰구간: 7.3개월 17.6개월) 이었고, 1년 생존율은 52%였다. 무진행생존기간의 중앙값은 3.0개월(95%신뢰구간: 1.6개월 -4.5개월)이며, 반응군에서의 중앙반응지속피간은 3.7개월(95% 신뢰구간: 3.0개월 - 4.4개월)이었다. 4) 60세 미만인 경우(20.1 months vs 6.6 months. p=0,0105), 조직학적 아형이 선암일 경우(25.6 months vs 7.9 months, 0=0.0055) 통계적으로 유의한 생존기간의 증가가 있었다. 5) 부작용으로 3도 이상의 백혈구 감소증은 12명(38.7%),호중구 감소증에 동반된 발열은 6명(19.3%),감염이 동반된 호중구 감소증은 4명(12.9%)에서 발생했다. 치료와 관련되어 1명이 사망하였다. 6) Docetaxel 용량에 따른 생존기간의 차이나 독성의 차이는 없었다. 결론 : Platinum을 근거로 하는 항암화학요법으로 치료받은 후 재발 또는 진행성 병변을 보이는 비소세포폐암환자들에게 docetaxel을 투여하는 것은 비교적 안전하고 효과적인 항암치료법으로 사료된다.

A Case of Non-Cardiogenic Pulmonary Edema and Pericardial Effusion Following the First Cycle of Docetaxel Chemotherapy

김형우,김도연 동국대학교 의학연구소 2008 東國醫學 Vol.15 No.1

Docetaxel치료 시 체액 저류 현상은 축적 용량과 관련되어 있는데, 아직까지 docetaxel을 이용한 첫번째 항암치료 후 체액 저류 현상이 있는 경우는 없었다. 국소적으로 진행된 비인두 암을 가진 47세 남자 환자가 docetaxel을 포함한 선행 보조 항암요법 치료 후 비심인성 폐부전과 심낭삼출을 주소로 내원하였다. 환자는 항암 치료 전 덱사메타손 전 처치를 시행 받았다. 항암 치료 10일 후, 그는 마른 기침과 가래, 운동시 호흡곤란을 호소하였다. 흉부 사진 결과 폐부종 및 흉막삼출, 그리고 심초음파 결과 중등도 심낭삼출이 있었다. 환자는 3일간 이뇨제와 덱사메타손 치료를 받았고, 보존적인 치료 후 회복되었다. 저자는 docetaxel을 포함한 첫번째 항암 치료 후 비심인성 폐부종과 심낭삼출 같은 체액 저류 현상을 보고하는 바이다. The development of fluid retention on docetaxel appears to be related to the cumulative dose, and no case of fluid retention has been reported after the first cycle of docetaxel chemotherapy. The authors describe the case of 47 year-old man with locally advanced nasopharyngeal cancer, who developed non-cardiogenic pulmonary edema and pericardial effusion after the first cycle of a docetaxel containing chemotherapy. The patient was administered the first cycle of neoadjuvant docetaxel containing chemotherapy with dexamethasone premedication. At 10 days after chemotherapy, he started complaining of a cough, non productive sputum, and dyspnea on exertion. A chest X-ray revealed pulmonary edema and pleural effusion, and echocardiography revealed moderate pericardial effusion with the maintenance of systolic and diastolic functions. The patient was treated with loop diuretics and dexamethasone for 3 days, and recovered after supportive management. The authors suggest that fluid retention, such as, non cardiogenic pulmonary edema and pericardial effusion can follow even the first cycle of docetaxel.

East Asian Subgroup Analysis of a Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-small Cell Lung Cancer Following Disease Progression after One Prior Platinum-Based Thera

박근칠,김주항,조은경,강진형,Jin-Yuan Shih,Annamaria Hayden Zimmermann,Pablo Lee,Ekaterine Alexandris,Tarun Puri,Mauro Orlando 대한암학회 2016 Cancer Research and Treatment Vol.48 No.4

Purpose REVEL demonstrated improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) with docetaxel+ramucirumab versus docetaxel+placebo in 1,253 intent-to-treat (ITT) stage IV non-small cell lung cancer patients with disease progression following platinum-based chemotherapy. Results from the East Asian subgroup analysis are reported. Materials and Methods Subgroup analyses were performed in the East Asian ITT population (n=89). Kaplan-Meier analysis and Cox proportional hazards regression were performed for OS and PFS, and the Cochran-Mantel-Haenszel test was performed for response rate. Results In docetaxel+ramucirumab (n=43) versus docetaxel+placebo (n=46), median OS was 15.44 months versus 10.17 months (hazard ratio [HR], 0.762; 95% confidence interval [CI], 0.444 to 1.307), median PFS was 4.88 months versus 2.79 months (HR, 0.658; 95% CI, 0.408 to 1.060), and ORR was 25.6% (95% CI, 13.5 to 41.2) versus 8.7% (95% CI, 2.4 to 20.8). Due to increased incidence of neutropenia and febrile neutropenia in East Asian patients, starting dose of docetaxel was reduced for newly enrolled East Asian patients (75 to 60 mg/m2, n=24). In docetaxel+ramucirumab versus docetaxel+placebo, incidence of neutropenia was 84.4% versus 72.7% (75 mg/m2) and 54.5% versus 38.5% (60 mg/m2). Incidence of febrile neutropenia was 43.8% versus 12.1% (75 mg/m2) and 0% versus 7.7% (60 mg/m2). Conclusion Results of this subgroup analysis showed a trend favoring ramucirumab+docetaxel for median OS, PFS, and improved ORR in East Asian patients, consistent with ITT population results. Reduction of starting dose of docetaxel in East Asian patients was associated with improved safety.

SNU-484 위암 세포주를 이종이식한 Nude Mouse에 Docetaxel과 Capecitabine 복합항암 화학요법을 하는 경우 Docetaxel 투여방법의 변화에 따른 Thymidine Phosphorylase의 유도와 항암효과 상승기전에 관한 연구

서상범(Sang Beom Suh),서병조(Byoung Jo Suh),김준희(Joon Hee Kim),유항종(Hang Jong Yoo) 대한외과학회 2007 Annals of Surgical Treatment and Research(ASRT) Vol.73 No.4

Purpose: Docetaxel (Taxotere<SUP>ⓡ</SUP>) and capecitabine are used in combination to treat advanced gastric cancer. Thymidine phosphorylase (TP) is an essential enzyme for the activation of capecitabine in tumors. This study sought to identify the best combination therapy with capecitabine and using two different schedules for docetaxel, a TP up-regulator, to enhance capecitabine’s efficacy. Methods: The human gastric cancer cell line SNU-484 was cultured and docetaxel (2㎍/㎖) was added to the 24-well plates that contained 5×105 cells/well. The total RNA was isolated and RT-PCR was done to identify the TP expression. Four- or five-week-old BALB/c-nu/nu mice were subcutaneously inoculated with the SNU-484 cells. The nude mice were divided into two groups and they were given capecitabine 539 ㎎/㎡ p.o. from days 1 to 14: Group 1 was given docetaxel 15 ㎎/㎡ i.v. on day 1; Group 2 was given docetaxel 7.5㎎/㎡ on days 1 and 8. Tumor tissues were excised on days 1, 8 and 15 to measure the TP and bcl-2 levels. Results: TP was expressed 2 hours after docetaxel administration. Group 2 had a higher TP concentration in the tumor tissues and a better antitumor effect than did Group 1. There was no difference in the bcl-2 concentration in the two groups. Conclusion: These results suggest that docetaxel stimulates the TP expression in tumor tissues and it enhances the antitumor activity of capecitabine. A weekly docetaxel injection with capecitabine administration can be used to treat gastric cancer more effectively than when docetaxel is injected once per cycle. Capecitabine had no bcl-2 suppressive effect in this study.

Elevated Prx1 Provides Resistance to Docetaxel, But Is Not Associated with Predictive Significance in Lung Cancer

( Ki Eun Hwang ),( Chul Park ),( Chang Hwan Seol ),( Yu Ri Hwang ),( June Seong Hwang ),( Jae Wan Jung ),( Keum Ha Choi ),( Eun Taik Jeong ),( Hak Ryul Kim ) 대한결핵 및 호흡기학회 2013 Tuberculosis and Respiratory Diseases Vol.75 No.2

Background: This study was conducted in order to elucidate the effects of docetaxel on the growth of peroxiredoxin 1 (Prx1) knockdown A549 xenograft tumors and further tested the role of Prx1 as a predictor for how a patient would respond to docetaxel treatment. Methods: Effects of docetaxel on the growth of scrambled- and shPrx1-infected A549 xenograft tumors in nude mice were measured. Moreover, immunohistochemical expression of Prx1 was evaluated in paraffin-embedded tissues from 24 non-small cell lung cancer patients who had received docetaxel-cisplatin regimens as a first-line treatment. Results: Docetaxel treatment in Prx1 knockdown xenograft tumor resulted in reduced tumors growth compared with other groups. Prx1 knockdown increased the production of cleaved caspases-8 and -9 in the control itself compared to scramble tumors. Moreover, docetaxel treatment in Prx1 knockdown tissue led to an increased protein band. Phosphorylated Akt was found in Prx1 scramble tissues. Phosphorylated FOXO1 was detected in the docetaxel treatment group. On the other hand, Prx1 knockdown completely suppressed the Akt-FOXO1 axis. The median progression free survival (PFS) of patients with low Prx1 expression was 7 months (95% confidence interval [CI], 6.0?7.7), whereas the median progression-free survival of patients with high Prx1 expression was 4 months (95% CI, 4.0?5.0). However, high Prx1 expression was not associated with decreased PFS (p=0.114). Conclusion: Our findings suggest that elevated Prx1 provides resistance to docetaxel treatment through suppression of FOXO1-induced apoptosis in A549 xenograft tumors, but may not be related with the predictive significance for response to docetaxel treatment.

Docetaxel-aggravated psoriasis in a patient with prostate cancer

( Seungkeol Yang ),( Bo Ri Kim ),( Chong Won Choi ),( Sang Woong Youn ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.1

Docetaxel is an anti-microtubule drug used to treat a variety of solid tumors, which makes it one of the most widely used chemotherapeutic agents. Various adverse effects have been reported with the use of docetaxel including skin toxicity, which manifests as hand-foot syndrome and radiation recall dermatitis. Although chemotherapeutic agent-induced psoriasis and its aggravation are relatively well-known conditions, only 2 cases of docetaxel-induced psoriasis have been reported despite its widespread use. A 78-year-old man with 50-year history of psoriasis presented with generalized erythematous scaly plaques involving his scalp and face. For over 5 years, psoriatic lesions had been confined to the hands and feet and controlled with the use of only topical agents. Three days prior to the emergence of current rash, he was administered the first dose of docetaxel as a treatment for prostate cancer. Given his past medical history and clinical features, we concluded that it was an exacerbation of his pre-existing psoriasis induced by the newly introduced docetaxel. Docetaxel was promptly discontinued and we started the treatment with acitretin, antihistamines, and topical calcipotriol/betamethasone dipropionate. The lesion began to improve and following 10 weeks of acitretin administration, his condition was controlled without aggravation of lesions. Herein, we describe a rare case of docetaxel-induced aggravation of psoriasis.

Comparative In Vitro Toxicity Study of Docetaxel and Nanoxel, a Docetaxel-Loaded Micellar Formulation Using Cultured and Blood Cells

Do, Van Quan,Park, Kwang-Hoon,Park, Jung-Min,Lee, Moo-Yeol Korean Society of ToxicologyKorea Environmental Mu 2019 Toxicological Research Vol.35 No.2

Nanoxel-$PM^{TM}$ (Nanoxel) is a docetaxel-loaded methoxy-poly(ethylene glycol)-block-poly(D,L-lactide) (mPEG-PDLLA). This newly developed and marketed nanoformulation exhibits an improved pharmacokinetic profile, efficacy, and safety. Although the safety of Nanoxel to docetaxel as well as its bioequivalence must be clinically confirmed, all biological activities have not been examined in in vitro or in vivo studies. Here, the toxicity in a cultured cell system and the effects on blood cells were tested with Nanoxel and docetaxel. The in vitro cytotoxicity of Nanoxel was found to be comparable to or slightly lower than that of docetaxel depending on the concentrations tested or the cell types. Neither docetaxel nor Nanoxel induced erythrocytes hemolysis and produced reactive oxygen species up to $100{\mu}M$. However, Nanoxel was able to enhance the aggregatory response of platelets to collagen, whereas docetaxel attenuated such aggregation in a range of $50-100{\mu}M$, while thrombin-induced aggregation was not affected by either of them. Docetaxel or Nanoxel did not alter basal level of $Ca^{2+}$ and 5-hydroxytryptamine-evoked $Ca^{2+}$ transient in vascular smooth muscle cells. These results suggest that the mPEG-PDLLA micellar formulation alters the toxicological properties of docetaxel, and that extra cautions are needed when evaluating the safety of nanomedicine.

Effects of formulation on pharmacokinetics of docetaxel in rats

Park, Jung-Hyun,Kim, You-Jin,Kwon, Kyoung-Eun,Lee, Seul-Gee,Lee, Byung-Koo,Lee, Hwa-Jeong 한국약제학회 2012 Journal of Pharmaceutical Investigation Vol.42 No.1

The aim of this study was to investigate the effects of formulation vehicles on the pharmacokinetics of docetaxel. The following three formulations of docetaxel were prepared to compare the pharmacokinetic profiles of docetaxel: Tween$^{(R)}$ 80 formulation (a vehicle composition of Taxotere$^{(R)}$), Cremophor$^{(R)}$ EL formulation (a vehicle composition of Taxol$^{(R)}$) and DMSO formulation (a combination of surfactants and solvents). Three different formulations of docetaxel were injected into the femoral vein of each rat at a dose of 5 mg/kg. Docetaxel and internal standard (IS, paclitaxel) were extracted from plasma by one-step extraction with acetonitrile. Docetaxel and IS were eluted at 13.0 min and 15.7 min in rat plasma, respectively, without interfering peaks from the endogenous components. Docetaxel was highly distributed to body organs and cleared from the body quickly with a short elimination half-life in Tween$^{(R)}$ 80 formulation. In Cremophor $^{(R)}$ EL formulation and DMSO formulation, systemic exposure (AUC) and maximum plasma concentration of docetaxel were enhanced 6-fold and 4-fold, respectively, as compared with Tween$^{(R)}$ 80 formulation after IV injection. These results suggest that the disposition patterns of docetaxel could be affected by formulation vehicles following IV injection.