The efficacy of cefepime (Maxipime) in the treatment of abdominal sepsis in surgical patients]

The efficacy of cefepime in the treatment of 46 patients operated for general peritonitis of various genesis and severity (APACHE II not greater than 35) was studied. Cefepime was used in a dose of 2 g administered every 12 hours as slow intravenous infusions in 0.9 per cent sodium chloride solution in combination with metronidazole administered intravenously in a dose of 7.5 mg/kg body weight. The treatment course was 4 to 15 days. 45 patients were given diflucan for the prophylaxis of fungal superinfection, 3 patients were given aminoglycoside antibiotics (netilmicin or amikacin) and 2 patients were given vancomycin per os. The favourable clinical effect of the cefepime therapy was stated in 38 patients (82.6 per cent) including 4 out of 10 patients with initial APACHE II > 15. 101 isolates of aerobic gram-negative and gram-positive microbes from 38 patients treated with cefepime in combination with metronidazole were tested to estimate the bacteriological efficacy of the therapy and it was shown that only 5.9 per cent of them was resistant. The pathogen eradication was stated in 84.2 per cent of the patients.     

Systemic availability and abortion-inducing effects of nocloprost after intravenous, subcutaneous and intragastric administration to pregnant guinea pigs

Nocloprost was administered to 3 groups of 4 pregnant guinea pigs intravenously and subcutaneously in a dose of 30 micrograms/kg and intragastrically in a dose of 100 micrograms/kg. Plasma nocloprost levels were measured at defined times up to 24 h p. adm. with a specific radioimmunoassay and induction of abortion monitored simultaneously. In one animal per group uterus pressure was recorded continuously up to 8 hours p.adm. Animals were sacrificed 7 days p.adm. and the number and state of fetuses in utero evaluated. Systemic availability of unchanged drug was 100% after intravenous (AUCi.v. = 8.6 +/- 2.0 ng h/ml) and subcutaneous (AUCs.c. = 11.5 +/- 1.2 ng h/ml) administration and approximately 30% after intragastric administration (AUCi.g. = 8.9 +/- 2.0 ng h/ml). The incidence of abortion after intragastric administration corresponded to that after subcutaneous administration. After intravenous injection the abortion rate was somewhat less, indicating that equal AUC-values do not necessarily indicate identical pharmacological effects.     

Efficacy of pefoxacin (abactal) in the complex treatment of patients with pancreonecrosis]

The efficacy of pefloxacin in the complex treatment of 28 patients with pancreatonecrosis of various etiology was estimated in a prospective trial. The diagnosis of pancreatonecrosis was verified by the data of the disease clinical progress, laboratory findings and instrumental examination. Pefloxacin (Abactal; LEK) was administered intravenously in a dose of 400 mg every 8 hours (1200 mg) in combination with metronidazole in a dose of 1.5-2.0 g a day intravenously. When indicated 3 days after the start of the pefloxacin therapy, the treatment was switched to the oral use of the drug in the same dosage. The positive clinical effect (cure and improvement) at the end of the treatment with pefloxacin was stated in 78 per cent of the patients in spite of the initial severity state of above 15 APACHE II. It was shown that in the treatment of patients with pancreatonecrosis when the severity state was not above 12 APACHE II the antibacterial therapy with pefloxacin in combination with metronidazole was optimal.     

Single dose cefotaxime plus metronidazole versus three dose cefuroxime plus metronidazole as prophylaxis against wound infection in colorectal surgery: multicentre prospective randomised study.

OBJECTIVE--To establish whether a single preoperative dose of cefotaxime plus metronidazole was as effective as a standard three dose regimen of cefuroxime plus metronidazole in preventing wound infection after colorectal surgery. DESIGN--Prospective randomised allocation to one of two prophylactic antibiotic regimens in a parallel group trial. Group sequential analyses of each 250 patients were performed. SETTING--14 District general and teaching hospitals. PATIENTS--1018 Adults having colorectal operations were randomised, of whom 943 were evaluated. Demographic features, conditions requiring surgery, and operative procedures were similar in the two groups. Most patients had surgery for carcinoma of the colon or rectum. INTERVENTIONS--Group 1 received cefotaxime 1 g intravenously plus metronidazole 500 mg intravenously preoperatively. Group 2 received cefuroxime 1.5 g intravenously plus metronidazole 500 mg intravenously preoperatively, followed by cefuroxime 750 mg intravenously plus metronidazole 500 mg intravenously eight hours and 16 hours postoperatively. MAIN OUTCOME MEASURES--Development of surgical wound infection (as evidenced by the presence of pus), death, or discharge from hospital. RESULTS--Wound condition was scored on a five point scale on alternate days until discharge or for up to 20 days postoperatively. Wound infection rates were: group 1, 32/453 (7.1%; 95% confidence interval 4.7% to 9.4%); group 2, 33/454 (7.3%; 95% confidence interval 4.9% to 9.6%). Death rates (group 1: 26/470 (5.5%); group 2: 31/471 (6.6%], the incidence of postoperative complications, the median duration of hospital stay (12 days), and antibiotic tolerance were all similar in the two groups. Pooled data from groups 1 and 2 showed that wound infections were more frequent when minor faecal contamination had occurred at operation and when the duration of operation exceeded 90 minutes (greater than 90 min 11.2% of cases; less than 90 min 4.8%) and were associated with an extended hospital stay. CONCLUSIONS--A single preoperative dose of cefotaxime plus metronidazole is an efficacious as a three dose regimen of cefuroxime plus metronidazole in preventing wound infection after colorectal surgery and has practical advantages in eliminating the need for postoperative antibiotics.     

A method for maintaining normoglycemia during labour and delivery in insulin-dependent diabetic women.

The effectiveness of combining the subcutaneous administration of short- and intermediate-acting insulin with the intravenous infusion of glucose in maintaining normoglycemia during labour and delivery in insulin-dependent diabetic women was tested. Fifty women were given intermediate-acting insulin twice daily in doses that were fractions of their usual dose, based on the projected duration of labour. In addition, they were given regular (i.e., short-acting) insulin every 6 hours, the dose being 1% of their total daily insulin dose for every increase of 10 mg/dl above 100 mg/dl (5.6 mmol/l) in the plasma glucose level 1 hour previously; the levels were measured every 3 hours. All the patients were fasting and received a basal intravenous infusion of 6 g/h of glucose; the rate of infusion was increased by 1 g/h for every decrease of 10 mg/dl in the plasma glucose level below 100 mg/dl. The mean plasma glucose levels (+/- standard deviation) were 90 +/- 46 mg/dl after 3 hours of labour, 92 +/- 35 mg/dl after 6 hours, 97 +/- 49 mg/dl after 9 hours and 107 +/- 65 mg/dl after 12 hours. With only one exception, in a premature infant, the 5-minute Apgar scores were identical to those of the infants of nondiabetic women.     

Single dose versus daily intravenous aminohydroxypropylidene biphosphonate (APD) for the hypercalcaemia of malignancy

Thirty patients with hypercalcaemia and known malignant disease were randomly allocated to receive 60 mg 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate (APD) intravenously as a single dose or as consecutive daily doses of 30 mg (two days) or 15 mg (four days). The rate of infusion was the same for each regimen (7.5 mg/hour). Calcium concentrations fell in all patients and returned to normal in all but two. Relapse of hypercalcaemia occurred after a mean of 21 days in each group. Urinary calcium excretion fell in all groups and symptoms were greatly improved. After relapse patients were retreated with APD (30 mg as a single infusion) and normocalcaemia maintained by regular infusions at two to three week intervals.APD given as a single 60 mg infusion over eight hours together with rehydration is recommended as the initial management of the hypercalcaemia of malignancy, followed by 30 mg APD roughly every two to three weeks to maintain normal or near normal serum calcium concentrations.     

高负荷剂量氯吡格雷联合替罗非班在非ST段抬高型急性冠状动脉综合 征患者经皮冠状动脉介入中的应用

目的：探讨高负荷剂量氯吡格雷联合替罗非班在高危非ST 段抬高型急性冠状动脉综合征（acute coronary syndrome,ACS） 患者经皮冠状动脉介入治疗（percutaneous coronary intervention,PCI）中的作用及安全性。方法：入选208 例高危非ST 段抬高型 ACS患者,根据PCI术前氯吡格雷负荷量不同,随机分为观察组和对照组。对照组：112 例,以氯吡格雷300 mg+ 替罗非班(用法同 观察组)治疗,观察组：96例,以氯吡格雷600 mg +替罗非班0.4 滋g/(kg·min)在30 min 内静脉注射。继以0.1 g/(kg·min)由微量泵 静脉持续泵入至手术后36 h,分别测定两组最大血小板聚集率(MPAR)变化、PCI 术后TIMI心肌灌注分级(TMPG);随访住院期间 和30 d内不良心血管事件和出血事件。结果：两组临床情况、PCI前负荷剂量氯吡格雷给药时间、支架置入数目比较差异无统计 学意义(P>0.05);用药后2 h、6 h、术后24 h两组MPAR均较用药前明显降低(P<0.05);用药后6 h两组MPAR 均低于用药后2 h (P<0.05);用药后2 h时观察组MPAR 低于对照组(P<0.05)。PCI术后TMPG 3级获得率观察组高于对照组(P<0.05);30 d内复合心 血管事件发生率、出血并发症两组比较差异均无统计学意义(P>0.05)。结论：PCI术前负荷氯吡格雷600 mg可以更有效、更迅速地 抑制患者的MPAR,联合应用替罗非班时仍可改善心肌灌注,且安全可行。     

Ciprofloxacin in the prevention and treatment of surgical infections]

A clinico-laboratory study on ciprofloxacin made by Bayer (Germany) was applied to patients with extended posttraumatic wounds and performed with the aim of preventing postoperative purulent complications in patients operated on the organs of the gastrointestinal tract. In the both groups ciprofloxacin was administered orally in doses of 500 and 1000 mg and intravenously in a dose of 200 mg. The results of the assay on ciprofloxacin sensitivity of the isolates from the wound excretion and urine showed that they were more sensitive to ciprofloxacin than to aminoglycosides and cephalosporins. 15 minutes after the intravenous administration the serum concentration of ciprofloxacin amounted to 7.5 +/- 0.9 micrograms/ml and in 6 hours it was equal to 0.45 +/- 0.45 micrograms/ml, the mean concentrations of ciprofloxacin being attained in the bile (8.7 +/- +/- 3.9 micrograms/ml), gallbladder wall (5.5 +/- 3.8 micrograms/g), liver (0.73 micrograms/g), muscles (1.93 micrograms/g) and tendon (0.15 microgram/g). After the oral administration in a dose of 500 mg ciprofloxacin was detected in the blood serum in an amount of 2.0 +/- 0.7 micrograms/ml in 1 hour and in an amount of 0.9 +/- 0.13 micrograms/ml in 6 hours. After the drug oral administration in a dose of 1000 mg the maximum concentrations were: 6.34 +/- 4.2 micrograms/ml on the average and 2.1 +/- 0.8 micrograms/ml in 6 hours (0.4 micrograms/g in the muscles, 1.4 micrograms/g in the skin and 0.34 micrograms/g in the bones). The study showed that ciprofloxacin was a highly efficient antimicrobial agent in the treatment of the complicated wound infections and the prophylaxis of the purulent complications during the postoperative period in the patients operated on gastrointestinal organs.     

不同剂量氯吡格雷治疗急性ST 段抬高心肌梗死的疗效及安全性分析

目的:探讨不同剂量氯吡格雷治疗急性ST段抬高心肌梗死(STEMI)的疗效及安全性。方法:178例急性STEMI患者随机分为高剂量组和常规剂量组,每组各69例。两组均给予阿司匹林、静脉溶栓、抗凝及降脂等常规治疗,高剂量组和常规剂量组分别口服氯吡格雷负荷量600 mg、300 mg,之后两组患者给予维持量75 mg/d。结果:治疗30 d后,高剂量组总有效率为91.0%,常规剂量组为77.5%,差异有统计学意义(P<0.05);高剂量组治疗后36 h及30d的MACE发生率为3.4%和6.7%,常规剂量组为12.4%和18.0%,差异均有统计学意义(P<0.05);两组出血发生率分别为9.0%,5.6%,差异无统计学意义(P>0.05)。结论:高剂量(600 mg)氯吡格雷治疗急性STEMI疗效优于常规剂量(300 mg),且具有良好的安全性。     

Clinico-laboratory basis for the endolymphatic use of beta-lactam antibiotics in pulmonology

Clinical efficacy and effect of cefuroxime, claforan and pentrexyl used endolymphatically were studied in 85 patients with acute abscess forming and persisting pneumonia. Previous routine antibiotic therapy in these patients was little effective. Administration of the antibiotics into the peripheral lymph nodes provided blocking of the lymphagenic pathway for the infection due to high levels in the lymphatic system. Endolymphatic use of cefuroxime and claforan resulted in a significant improvement of the functions of the T- and B-immunity systems and the indices of natural resistance. The levels of the autoimmune reactions and sensitization to the bacterial antigens decreased. Endolymphatic use of cefuroxime and claforan once every 3 days provided recovery of 9 2.8 per cent of the patients, the treatment periods being decreased 2.5--3 times. Intravenous administration of the drugs according to the routine schemes, endolymphatic use of pentrexyl (5 g once every 3 days) and endolymphatic administration of cefuroxime in a single dose followed by intravenous therapy was less effective. The efficacy of pentrexyl increased, when it was used endolymphatically in combination with lysozyme. Endolymphatic use of claforan in doses of 2--3 g once every 3 days (3--4 infusions during the treatment course) was most effective.     

Intradermal administration of lipopolysaccharide in treatment of human cancer

 Lipopolysaccharide (LPS) has been recognized as a potent antitumor agent in animal tumor models; however, its use in human cancer therapy has been limited to only one trial, in which LPS from Salmonella was given intravenously. It was not very successful because of poor tumor response and was also toxic. We originally developed LPS prepared from Pantoea agglomerans (LPSp), and this was a well-purified, small-molecular-mass (5 kDa) agent. We chose intradermal rather than intravenous administration in the hope that the former would release LPS slowly into the bloodstream, and thus be less toxic while preserving antitumor activity. In our animal tumor models, intradermal administration was indeed less toxic and more beneficial for tumor regression than intravenous administration. We made a pilot study with intradermal administration of LPSp on the treatment of ten advanced cancer patients. Five of them had evaluable tumor, which had failed earlier to respond to conventional chemotherapy. Cyclophosphamide was also administered in this trial, in anticipation of its synergistic effect with LPSp. In this study LPSp was injected intradermally into each patient twice a week, starting with an initial dose of 0.4 ng/kg, and raising it to 600 or 1800 ng/kg. A 400-mg/m² dose of cyclophosphamide was given intravenously every 2 weeks. After completion of the dose escalation, the treatment was continued for at least 4 months, and it was found that 1800 ng/kg LPSp was well tolerated. A significant level of cytokines was observed in the sera for at least 8 h. These results indicate higher tolerable doses and remarkably more continuous induction of the cytokines than were reported in a previous study by others using intravenous administration. Three of the five evaluable tumors showed a significant response to our combined therapy. Intradermally administered, LPS was less toxic and elicited a tumor response in combination with cyclophosphamide; it can thus can be applied to cancer treatment even in humans. Received: 3 August 1995 / Accepted: 2 April 1996     

Experience with maxipime in neurosurgical clinic]

Cefepime (Maxipime, Bristol-Myers Squibb), a 4th generation cephalosporin was used in the postoperative treatment of 121 patients of Anesthesiology and Intensive Care Unit of Neurosurgical Clinics. The patients were divided into groups by the risk factor of pyoseptic complications. The results were estimated by the number and nature of the complications such as increasing liquor neutrophilic cytosis, systemic inflammations and others. The findings (increasing liquor neutrophilic cytosis only in 2 patients and endobronchitis in 4 patients) and good tolerance of cefepime (Maxipime) were in favour of its use in a dose of 1 g administered intravenously dropwise during initial narcosis and in 12 hours as an efficient agent for perioperative prophylaxis in neurosurgical patients.     

Study of embryotoxic and teratogenic effects of amphotericin B and a methyl derivative of amphotericin B in rats after their intravenous and intra-amniotic administration]

The embryotoxic action of amphotericin B and its methyl derivative was compared in rats after their intravenous and intraamniotic administration. The concentrations of amphotericin B and its methyl derivative in the amniotic cavity on days 13, 14 and 15 of pregnancy were 1.5 and 36 micrograms/ml, respectively. When administered intravenously during the preimplantation period the antibiotics had no embryotoxic action. Intravenous administration of amphotericin B in a dose of 500 micrograms/kg and its derivative in a dose of 2000 micrograms/kg during organ genesis induced a decrease in the craniocaudal size. In a dose of 3000 micrograms/kg administered intravenously the methyl derivative of amphotericin B induced an increase in postimplantation death rates. Administration of amphotericin B to the amniotic cavity had no damaging action. Administration of the methyl derivative on day 15 of pregnancy led to anomalous development of the lower extremities and slower ossification. The threshold doses by the embryotoxic action for intravenous administration are 500 micrograms/kg for amphotericin B and 2000 micrograms/kg for the methyl derivative. Administration of the antibiotics to the amniotic cavity revealed potential teratogenic properties of the amphotericin B methyl derivative.     

Vaginally administered 16,16-dimethyl-PGE2 for the induction of midtrimester abortion

Thirty patients in the 13th–20th week of gestation underwent therapeutic abortion utilizing vaginally administered 16,16-dimethyl-PGE₂ (free acid) suppositories. The first 15 patients obtained individual doses in the range of 400–1200 μg given every three hours (mean total dose 4.2 mg). In the following 15 patients a fixed dose schedule was used (800 μg followed by 1000 μg every three hours; mean total dose 5.3 mg). All but one of the 30 patients aborted. The mean induction-abortion interval for all patients was 16.8±6.9 hours (mean ± S.D.) With the fixed dose regime the success rate was 100% and the induction-abortion interval 16.0±5.9 hours. Because gastro-intestinal side effects were minimal, neither anti-emetic nor anti-diarrheic medication was required. A slight elevation of temperature was noted in five patients. The uterine response to the vaginal administration of this compound was characterized by a gradual increase in uterine tonus followed by sustained stimulation. The results are interpreted to suggest that the vaginal administration of 16,16-dimethyl-PGE₂ is a useful alternate method for the induction of second trimester abortion. Moreover, this compound seems to cause fewer gastro-intestinal side effects than other prostaglandins administered by the vaginal route at our department.     

Continuous intravenous infusion versus intermittent administration of streptokinase in patients with deep venous thrombosis of the lower extremity]

In a multicenter randomized trial, the efficacy and safety of two streptokinase (SK) dosage regimens have been evaluated in patients with proximal deep vein thrombosis of inferior limbs. Twenty-nine patients received SK by a continuous intravenous infusion (250,000 IU as initial dose, 100,000 IU/h as maintenance dose), and 26 patients were treated with intermittent SK administration (500,000 IU as initial dose, followed by 250,000 IU every 12 h). Thrombolytic therapy was continued for 4 days, then the patients received heparin for 5 days and oral anticoagulant for 3 months. The results of treatment as judged by phlebographic examinations were similar in the two groups. Complete, substantial or partial thrombolysis was achieved in 52% of patients in the continuous infusion group and in 58% of patients in the intermittent treatment group. During SK administration, major bleeding complications occurred in 6 patients treated by continuous infusion and in 2 of the second group. The results showed that the intermittent SK administration is as effective and safe as the method of continuous SK infusion in the treatment of deep vein thrombosis.     

Prevention and treatment of postoperative pyoinflammatory complications and cefuroxime]

Antibacterial activity and efficacy of cefuroxime (ketocef, Pliva, Zagreb) in the treatment and prophylaxis of surgical infections in a general hospital and particularly in the unit of vessel and aorta surgery, the unit of lung surgery and the unit of microsurgery were estimated. The study included 57 patients (43 males and 14 females) at the age of 21 to 70 years. Cefuroxime was administered intravenously in a dose of 1.5 g followed by its intramuscular administration in a dose of 750 mg with an interval of 8 hours. The results showed that cefuroxime was effective in the treatment (80 per cent) and prophylaxis (93.6 per cent) of the pyo-inflammatory complications and was active against the majority of the surgical infection pathogens.     

高负荷剂量氯吡格雷联合替罗非班在非ST段抬高型急性冠状动脉综合征患者经皮冠状动脉介入中的应用

目的：探讨高负荷剂量氯吡格雷联合替罗非班在高危非ST段抬高型急性冠状动脉综合征（acute coronarysyndrome,ACS）患者经皮冠状动脉介入治疗（percutaneous coronary intervention,PCI）中的作用及安全性。方法：入选208例高危非ST段抬高型ACS患者,根据PCI术前氯吡格雷负荷量不同,随机分为观察组和对照组。对照组：112例,以氯吡格雷300 mg＋替罗非班（用法同观察组）治疗,观察组：96例,以氯吡格雷600 mg＋替罗非班0.4μg/（kg·min）在30 min内静脉注射。继以0.1 g/（kg·min）由微量泵静脉持续泵入至手术后36 h,分别测定两组最大血小板聚集率（MPAR）变化、PCI术后TIMI心肌灌注分级（TMPG）;随访住院期间和30 d内不良心血管事件和出血事件。结果：两组临床情况、PCI前负荷剂量氯吡格雷给药时间、支架置入数目比较差异无统计学意义（P〉0.05）;用药后2 h、6 h、术后24 h两组MPAR均较用药前明显降低（P〈0.05）;用药后6 h两组MPAR均低于用药后2 h（P〈0.05）;用药后2 h时观察组MPAR低于对照组（P〈0.05）。PCI术后TMPG 3级获得率观察组高于对照组（P〈0.05）;30 d内复合心血管事件发生率、出血并发症两组比较差异均无统计学意义（P〉0.05）。结论：PCI术前负荷氯吡格雷600 mg可以更有效、更迅速地抑制患者的MPAR,联合应用替罗非班时仍可改善心肌灌注,且安全可行。     

Efficacy of meropenem in the treatment of severe complicated urinary tract infections]

The clinical and bacteriological efficacies of meropenem in the treatment of 12 patients with urinary tract infection were studied. In 8 patients the drug was administered intravenously in a dose of 1 g every 8 hours and in 4 patients with the creatinine clearance below 50 ml/min it was administered in a dose of 1 g every 12 hours (the treatment course of 7 to 10 days). Meropenem was used in the monotherapy. Severe complicated urinary tract infections were mainly observed in the patients with long-term urolithiasis, subjected to repeated surgical interventions and isolating as a rule polyresistant strains of Pseudomonas aeruginosa and E.agglomerans as the pyelonephritis pathogens at a titre of 5 x 10(5)-5 x 10(8) microbial cells per 1 ml of the urine susceptible to meropenem in 80 to 96 per cent of the cases. The clinical efficacy of the drug was stated in all the patients while the bacteriological efficacy amounted to 88.9 per cent.     

Serial intramuscular injections of 15(S)-15-methyl-prostaglandin F2α in the induction of abortion

Abortion was successfully induced in 62 of 68 patients in the 9th to the 26th week of pregnancy by serial intramuscular administration of 15(S)-15-methyl-prostaglandin F_2α (15-ME-PGF_2α). In 6 patients who failed to abort after 24 hours of prostaglandin administration, a concomitant infusion of oxytocin was initiated; 5 of these patients aborted within 12 hours of the combined therapy. A single patient failed to abort, even with the combined therapy, and underwent surgical evacuation. The mean abortion time in the 67 successful inductions was 14.56 hours. Parous patients aborted somewhat faster, mean 13.98 hours, as compared to nulliparous patients, mean 15.02 hours, but this difference was not statistically significant. In this study initial intramuscular injection of 100 μg 15-ME-PGF_2α was followed in 1 hour by 250 μg and then 250 μg every 2 hours with concomitant oxytocin therapy initiated after 24 hours. The results with this dose schedule were compared to the results obtained in a previous study with a higher dose schedule, an initial dose of 100 μg 15-ME-PGF_2α, followed in 1 hour by 250 μg then 500 μg every 2 hours. There was no significant difference in the mean abortion time and the incidence of side effects between the 2 dose schedules. The mean abortion time for patients with gestational ages of 16 weeks and less was the same with both dose schedules, however patients with gestational ages of 17 weeks and higher aborted somewhat faster with the higher dose schedule. It might therefore be advisable for patients with gestations of 17 weeks and higher to be treated with the higher dose schedule. In earlier gestations patients could be started on the lower schedule, and if abortion had not occurred within 15 hours the dose of 15-ME-PGF_2α could then be increased to 500 μg every 2 hours.     

Biliary excretion of exogenous hematin in rats

Rats with bile fistula were injected intravenously with single doses of hematin (5,10,20,30, and 40 mg/kg body weight). Bile samples were collected every 30 min. for 4 hours, and at longer time intervals thereafter. The concentration of hematin in the bile was measured spectrophotometrically at 590 nm. The maximal hematin concentration in the bile (0.29 mg/ml for 40 mg/kg) observed 1.25 hours (average from 15 rats; range 0.5 – 1.5 hours) after hematin administration occured progressively later for lower doses of hematin, and for 5 mg/kg was observed at 3.14 hours (average for 4 rats; range 2–4 hours). The total hematin excreted within 4 hours was 8.0% of injected dose for 40 mg/kg and is dose dependent.