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Bidirectional chemotherapy may provide in addition adequate drug concentrations from the side of the subperitoneal space to the peritoneal tumour nodules. Major pharmacological problems of intraperitoneal chemotherapy are limited tissue penetration and poor homogeneity of drug distribution to the entire seroperitoneal surface. Significant pharmacological determinants of intraperitoneal chemotherapy are choice of drug, drug dosage, solution volume, carrier solution, intra-abdominal pressure, temperature, duration, mode of administration, extent of peritonectomy and interindividual variability. Drugs most commonly applied for intraperitoneal chemotherapy include mitomycin C, cisplatin, carboplatin, oxaliplatin, irinotecan, 5-fluoruracil, gemcitabine, paclitaxel, docetaxel, doxorubicin, premetrexed and melphalan. The drugs and their doses that are used vary widely among centres. While the adequate drug choice for intraperitoneal and bidirectional chemotherapy is essential, randomized clinical trials to determine the most optimal drug or drug combination are lacking, and only eight retrospective comparative clinical studies are available. Further clinical pharmacological studies are required to determine the most effective drug regimen for intraperitoneal and bidirectional chemotherapy in various indications. In the future, reliable drug sensitivity testing and genetic profiling of peritoneal metastases will be needed for enabling patient-specific therapy.<\/jats:p>","DOI":"10.1515\/pp-2017-0010","type":"journal-article","created":{"date-parts":[[2017,5,3]],"date-time":"2017-05-03T06:01:41Z","timestamp":1493791301000},"page":"47-62","source":"Crossref","is-referenced-by-count":103,"title":["Pharmacological principles of intraperitoneal and bidirectional chemotherapy"],"prefix":"10.1515","volume":"2","author":[{"given":"Eelco","family":"de Bree","sequence":"first","affiliation":[{"name":"Department of Surgical Oncology , Medical School of Crete University Hospital , Heraklion , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimosthenis","family":"Michelakis","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology , Medical School of Crete University Hospital , Heraklion , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitris","family":"Stamatiou","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology , Medical School of Crete University Hospital , Heraklion , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Romanos","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology , Medical School of Crete University Hospital , Heraklion , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odysseas","family":"Zoras","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology , Medical School of Crete University Hospital , Heraklion , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2017,4,29]]},"reference":[{"key":"2025120909204642540_j_pp-2017-0010_ref_001_w2aab3b7c19b1b6b1ab2b1b1Aa","doi-asserted-by":"crossref","unstructured":"Sugarbaker PH, Stuart OA, Vidal-Jove J, Pessagno AM, DeBruijn EA. 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