The importance of the PK-PD theory in various antibacterial therapy is reported. The PK-PD parameter in aminoglycosides (AGs) is considered to be Cmax/MIC and once-daily dosage (OD) is said to be more advantageous in clinical response and adverse effects suppression than multiple daily dosage (MDD). We compared the clinical response and adverse effects in OD and MDD groups for 362 cases administered. amikacin (AMK), dibekacin (DKB), gentamicin (GM), isepamicin (ISP), tobramycin (TOB) from January 1 to December 31 2006. In the MDD groups AMK and GM peak concentration were not effective. In the duration, in the OD groups GM and the MDD groups ISP were significantly short.(GM: p=0.0226, ISP: p=0.0263) No statistically significant difference was seen between groups in changes in peripheral white blood cell count or serum CRP or whether detected bacteria disappeared. No rise in SCr was seen in advers effects of ISP in the MDD groups.(p=0.0465) We are not able to prove a predicted difference from a PK-PD theory by the dosage and dosage interval that was clinical administered, but our results suggest that reexamination that included the increase dosage was necessary.
Fourth-generation cephems used as a first-line agent for febrile neutropenia, in Japan, are usually administrated twice a day. Administration three times a day has, however, proven to be more efficacious, although its cost benefit remains unknown. We conducted a prospective clinical trial using cefozopran (2g, 1g, and 1g, q8h) for febrile neutropenia from April to December 2006. Using clinical data from this trial, we determined the effective cost for one dose to be 63, 036 yen. Administration twice a day (2g, 2g, and q12h) cost 78, 327 yen. In conclusion, we found that administration three times is more effective than twice a day in cost and effectiveness. The cost antifungal agents must thus be studied more carefully.
A 51-year-old man diagnosed with acute lymphocytic leukemia, was treated with a multi-drug regimen including vincristine (VCR), along with itraconazole (ITCZ) as prophylaxis against potential fungal infections. He developed adverse reactions, included constipation, numbness of the extremities and hyponatremia, in addition to hepatic damage, all of which were thought to have resulted from the use of VCR, with ITCZ was discontinued, the fluid replacement volume was decreased along with sodium supplementation, and the patient's condition improved. Vinca alkaloids are metabolized by CYP3A4, an isoform of cytochrome P450. In this connection all of the azole antifungals are known to inhibit CYP3A4 inhibitors. In our case, the serious adverse reactions observed were thought to have resulted from the drug interactions between VCR and ITCZ which led to a delay in VCR metabolism.
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