Using indomethacin (IND) capsules (Caps) before the date of expiration, we conducted the dissolution tests that are prescribed in the 17th Revision Japanese Pharmacopoeia (JP 17) and found a preparation within a serial number (Lot) that failed to satisfy the specified dissolution rate. Thus, we investigated factors that decrease dissolution rates of IND Caps during storage at room temperature (r.t.). In elution profiles of IND Caps samples, dissolution rates decreased as the expiration date approached. Moreover, after extended elution of formulations with unacceptable 20 min dissolution rates, dissolution rates remained in less of those specified in JP 17. Moreover, changes in dissolution profiles of preparations with pending expiry did not reflect changes in Caps shells, suggesting changes in the active contents. However, IND contents of the offending preparations decreased very little, even under accelerated conditions. Thus, in further experiments, we investigated preservation conditions of IND Caps, and found that humidity greatly decreases dissolution rates, and preservation of press-through package (PTP) sheets were also suggested to affect IND Caps. Finally, we found that the use of aluminum bag packaging prevents decreases in dissolution rates of IND Caps.

No abstract

antibiotics are used to manage hemo-dialysis patients after hemodialysis. Using this protocol, the serum concentration of aminoglycoside antibiotics in such patients is kept at a higher level for a long time which thus induces a toxic effect of aminoglycoside antibiotics.We administered tobramycin (TOB) 90 mg to 2 dialysis patients with infectious disease before each hemodialysis, then TOB was removed from the patients by hemodialysis after several hours.One patient was given TOB 90 mg 17 times over 33 days without any symptoms of either ototoxicity or dizziness. Another patient was given TOB 90 mg 5 times over 13 days, and his infectious condition improved markedly.The administration of aminoglycoside antibiotics before hemodialysis was thus suggested to be safe and effective for the treatment of infectious diseases in dialysis patients.We analyzed the postantibiotic effect (PAE) and the postantibiotic effect subMIC effect (PASME) of TOB for Pseudomonas aeruginosa ATCC 27853 in vitro. As a result, higher concentrations of TOB (4 MIC) and a longer exposure to it were thus found to induce stronger PAE and PASME.We therefore recommend that aminoglycoside antibiotics be given before hemodialysis in dialysis patient, and thereafter they should be removed, by hemodialysis after several hours, because high concentrations of arninoglycosides in the serum for several hours can induce stronger PAE and PASME enhance the efficacy and safety of aminoglycoside in addition to its own bacteriocidal activity.

No abstract

This study discusses the possibility that human serum albumin(HSA)preparation has equal binding efficiency with drug to normal serum albumin.The binding percentage with theophylline(TH)in vitro was 61-64% in normal serum albumin,32% in HSA preparation,and 65% in dialyskl HSA preparation.This suggests that the fall of the binding percentage with TH in HSA preparation results not from the heat treatment but from the stabilizers. In addition,the influence of the change of pH value on the binding efficiency was equal in both normal albumin and HSA preparation,which suggests that the binding state of HSA preparation with TH is similar to that of normal serum albumin.