Mean Peak Serum Concentration Research Articles

Fluconazole: A New Triazole Antifungal Agent

Fluconazole is a fluorine-substituted, bis-triazole antifungal agent. Its mechanism of action, like that of other azoles, involves interruption of the conversion of lanosterol to ergosterol via binding to fungal cytochrome P-450 and subsequent disruption of fungal membranes. Activity against Aspergillus spp., Blastomyces dermatitidis, Candida spp., Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum, and Paracoccidioides brasiliensis has been demonstrated in several animal models. Fluconazole can be administered both orally and intravenously. Mean peak serum concentrations achieved in human volunteers after 50 and 100 mg (oral) are 3.1 and 7.0 mumols/L respectively. Protein binding is low (11 percent) and cerebrospinal fluid to serum ratio is 0.58 to 0.89. Serum half-life is long (22-32 hours) and elimination is via renal clearance of unchanged drug. Clinical trials and reports support the use of fluconazole in treatment of candidiasis, particularly oropharyngeal and esophageal infections in immunocompromised hosts. Fluconazole is also approved for initial and suppressive therapy of cryptococcal meningitis. Its role in management of systemic fungal infections will be further defined once results of other comparative trials become available. Fluconazole is well tolerated and its effects on steroidogenesis are markedly less than those of ketoconazole. Antipyrine clearance is not altered at low doses (50 mg) of fluconazole; however, drug interactions with the use of larger doses can be anticipated with agents such as cyclosporin, phenytoin, oral hypoglycemics, and warfarin. Rifampin appears to decrease metabolic clearance of fluconazole. Fluconazole is available as oral and parenteral formulations. Once-daily doses of 100-400 mg are recommended. Dosage reduction is advised for patients with impaired renal function.

Ampicillin and Sulbactam Pharmacokinetics and Pharmacodynamics in Continuous Ambulatory Peritoneal Dialysis (CAPD)

The fixed combination antibiotic ampicillin/sulbactam may provide a new, safe, and effective method of treating dialysis-related bacterial peritonitis. The pharmacokinetics of this antibiotic combination were determined in patients receiving continuous ambulatory peritoneal dialysis (CAPD). The pharmacodynamic activity of this drug was also determined by use of mean bactericidal titers against selected bacterial strains. Six noninfected CAPD patients in a randomized two-way crossover study were given a fixed dose of ampicillin (2 gm) and sulbactam (1 gm) either intravenously or intraperitoneally. The mean peak ampicillin and sulbactam serum concentrations following intravenous dosing were 170.3 and 87.5 micrograms/mL, respectively. The mean peak serum concentrations of ampicillin and sulbactam following intraperitoneal dosing were 48.0 and 27.8 micrograms/mL, respectively. Absolute bioavailabilities of the intraperitoneal ampicillin and sulbactam doses were 60% and 68%. Both drugs exhibited similar distribution and elimination characteristics. Renal failure markedly reduced drug elimination. Intraperitoneal administration of ampicillin/sulbactam provided satisfactory inhibitory and bactericidal antibiotic titers for most organisms in dialysate at 6 h but not 24 h. Ampicillin/sulbactam (2 gm/1 gm) should be administered every 12 h to patients with peritoneal dialysis-related peritonitis.

Steady State Pharmacokinetics and Dose‐Proportionality of Phenylpropanolamine in Healthy Subjects

The pharmacokinetics of phenylpropanolamine (PPA) were studied in five healthy male volunteers after single oral doses of 25, 50 and 100 mg of the drug as well as at steady state after seven, 4-hourly doses of PPA. The peak serum concentrations and AUC infinity values increased linearly with an increase in dose, whereas the time to reach peak serum concentrations did not vary significantly between doses. The half-life remained relatively constant with an increase in dose (t1/2 = 3.8 to 4.3 hours), as did renal clearance (ClR = 0.41 to 0.44 l/kg/h). The percentage of unchanged PPA excreted in the urine over a 14 hour period was 64%, 63% and 73% for the 25, 50 and 100 mg doses, respectively. The pharmacokinetics of PPA were found to be linear in the dosage range 25 to 100 mg. Steady state serum concentrations were significantly higher than single dose concentrations, with the mean peak serum concentration increasing from 113 ng/ml after a single dose to 183 ng/ml at steady state. The time at which these were attained decreased from 1.47 hours after a single dose to 0.73 hours at steady state. Both clearance and volume of distribution were significantly different after a single dose compared to steady state (P less than 0.05), whereas no significant differences were found between the other parameters.

Pharmacokinetics of oral zidovudine (azidothymidine) in patients with AIDS when administered with and without a high-fat meal

Zidovudine is the only drug currently approved for the treatment of HIV infection. The present recommended doses found to be efficacious in patients with AIDS (200 mg every 4 h) achieve serum zidovudine concentrations greater than 0.267 micrograms/ml (1 mumol/l). Since patients often take zidovudine with food, we have investigated the effect of a liquid high-fat meal on the rate of absorption of zidovudine and on the peak serum concentration achieved. Eight patients received their usual dose of zidovudine (100 mg or 250 mg), with and without a liquid high-fat meal, on two separate study days, in a randomized crossover fashion. Blood and urine samples were collected over a 4-h period. In the absence of food, zidovudine is rapidly absorbed; the time to reach maximal serum concentration (Tmax) was 0.68 (+/- 0.25) h and the mean peak serum concentration (Cmax) achieved was 0.49 (+/- 0.3) micrograms/ml (dose normalized to 100 mg dose). In the presence of a high-fat meal, Tmax was significantly prolonged [1.95 (+/- 0.69) h; P less than 0.05] and the Cmax reduced [0.245 (+/- 0.12) micrograms/ml; P less than 0.05]. This demonstrates that to achieve maximal zidovudine serum concentrations, patients should take this medication on an empty stomach.

Pharmacokinetics of once daily intra-peritoneal aztreonam and vancomycin in the treatment of CAPD peritonitis

The pharmacokinetics of aztreonam and vancomycin were studied in six adult patients who developed peritonitis during Continuous Ambulatory Peritoneal Dialysis. Aztreonam 3 g was added to the first exchange in each 24 h period with vancomycin 500 mg on the first day and 250 mg on each subsequent day (provided the pre-dose serum vancomycin concentration was less than 10 mg/l) for a total of ten days. Aztreonam and vancomycin concentrations were measured in the serum and dialysate at 1, 2, 6, 12, 18 and 24 h after the initial dose and pre-dose on days 5 and 10. By the end of the ten day study all patients had recovered clinically and had a normal dialysate. For aztreonam, the mean peak serum concentration was 84.3 mg/l (range 59.6-102.8), the mean 24 h pre-dose serum concentration was 23.0 mg/l (range 8.6-39.2) and the mean 24 h pre-dose dialysate concentration was 15.5 mg/l (range 5.0-32.0). For vancomycin, the mean peak serum concentration was 10.2 mg/l (range 8.1-12.6), the mean 24 h pre-dose concentration was 5.5 mg/l (range 3.6-6.4), and the mean 24 h pre-dose dialysate concentration was 3.4 mg/l (range 2.4-4.6). In the treatment of CAPD peritonitis, once daily intra-peritoneal administration of aztreonam 3 g with vancomycin 500 mg initially and 250 mg on subsequent days (serum concentrations permitting) provides concentrations of antibiotic in both the serum and dialysate throughout the 24 h period in excess of the inhibitory concentrations of those organisms most frequently encountered in this condition.

SERUM CONCENTRATIONS OF PRILOCAINE FOLLOWING RETROBULBAR BLOCK

Retrobulbar block for eye surgery is associated with adverse reactions. We performed retrobulbar block in 10 patients using prilocaine (Citanest) and found mean (SD) peak serum concentrations of 851 (165.6) ng ml-1 (range 540-1100 mg ml-1). Peak serum concentrations occurred 3-7 min after the end of administration of the block, and in all cases were less than those associated with toxicity.

The pharmacokinetics and inflammatory fluid penetration of orally administered azithromycin

The pharmacokinetics of azithromycin were determined during a 24 h period following oral administration of a single 500-mg dose to each of six male volunteers. Concentrations in serum, urine and cantharides-induced inflammatory fluid were determined by microbiological assay. The mean peak serum concentration of 0.45 mg/l was obtained at a mean time of 2.6 h post-administration. The elimination half-life from serum was seen to increase with time post-dose; the mean elimination half-life at 16 h post-dose was 9.6 h. Inflammatory fluid was penetrated rapidly, with the mean peak concentration of 0.13 mg/l achieved at a mean time of 3.25 h post-dose. After this peak, levels initially decreased, but after 8 h from drug administration until the end of the trial period, inflammatory fluid concentrations remained relatively constant. The mean inflammatory fluid penetration up to the end of the study period was 74%. The mean urinary recovery of azithromycin, during the initial 24 h post-dose, was 6%.

Pefloxacin efficacy in Gram-negative bacillary meningitis

Sixteen patients with acute meningitis caused by Gram-negative bacteria were treated with pefloxacin intravenously. The age range of the patient group was six months to 85 years with a mean age of 40 years; three patients were children. In all but two patients meningitis was a complication of neurosurgical operations and fourteen of the sixteen had received prior therapy which was not successful. The causative organisms were: Pseudomonas aeruginosa (5), Acinetobacter calcoaceticus (4), Klebsiella pneumoniae (3), Enterobacter cloacae (2), Citrobacter diversus (1) and Salmonella group C (1). Pefloxacin was administered intravenously 800 mg twice a day to the adult patients (mean dosage of 21( +/- 6.7) mg/kg body weight) for a mean period ( +/- S.D.) of 11( +/- 4) days. The mean cerebrospinal fluid concentration of pefloxacin was 8.8( +/- 5.0) mg/l which was 54% of the mean peak serum concentration (16.3( +/- 8.8]. The mean MIC and MBC of the causative organisms were 1.1( +/- 1.2) mg/l and 1.64( +/- 1.2) mg/l. Thirteen patients (87%) were cured or clinically improved and twelve (80%) were bacteriologically cured. One patient failed, another patient had reinfection and one was not assessable. No side effects were observed. In the present study pefloxacin offered an efficacious and safe treatment of Gram-negative meningitis following failure of other antibiotic therapy.

Ciprofloxacin (intravenous/oral) versus ceftazidime in lower respiratory tract infections

The efficacy and safety of intravenous ciprofloxacin was compared with intravenous ceftazidime in 80 hospitalized patients with lower respiratory tract infection. There were 40 patients in each treatment group. Patients and physicians were blinded to the randomized scheme for treatment groups until patient consent was obtained. The 37 evaluable ciprofloxacin-treated patients received 200 mg every 12 hours intravenously as initial therapy and 29 completed their course receiving oral ciprofloxacin. The 34 evaluable ceftazidime-treated patients received 1 to 2 g intravenously every eight to 12 hours. The two groups did not differ with respect to patient age, infection severity, and admitting diagnosis. Clinical outcomes were similar with greater than 95 percent of treatments in each group being successful. Headache was the most commonly reported complaint (four patients) in the ciprofloxacin group. Three patients experienced substantial increases in serum theophylline concentrations while receiving ciprofloxacin. The predominant pathogens isolated were Haemophilus influenzae and Pseudomonas aeruginosa, and susceptibility rates for all organisms were similar for both drugs. The mean peak serum concentration at steady state while receiving intravenous ciprofloxacin was 2.3 μg/ml, and the mean trough concentration was 0.5 μg/ml. Patients randomly assigned to ciprofloxacin therapy received 2.6 fewer days of intravenous antibiotic therapy than those receiving ceftazidime. This 80-patients comparative trial demonstrates that ciprofloxacin and ceftazidime are similar in efficacy and safety when treating gram-negative lower respiratory tract infections. There appears to be potential for cost-reducing benefits through decreased length of intravenous therapy and earlier hospital discharge.

Intravenous ciprofloxacin therapy in severe infections

Fifty evaluable patients (34 men and 16 women; mean age, 47 years) with severe infections were given intravenous ciprofloxacin (200 mg every 12 hours) for a mean of 14 days. Therapy was continued with oral ciprofloxacin 500 to 750 mg every 12 hours in 34 cases for a mean of 57 days. The sources of the infections were bone and joint (26 patients), respiratory tract (10 patients), urinary tract (four patients), soft tissue (four patients), abdominal (three patients), bacteremia of unknown origin (two patients), and right-sided endocarditis (one patient). Fifteen patients (30 percent) were bacteremic. Causative organisms included Pseudomonas aeruginosa (32 patients), other gram-negative bacilli (18 patients), and gram-positive cocci (nine patients). Minimal inhibitory concentrations ranged between 0.03 and 1 μg/ml. Mean peak serum concentrations were 1.58 μg/ml (intravenous) and 2 μg/ml (oral); mean trough serum concentrations were 0.23 μg/ml (intravenous) and 0.32 μg/ml (oral). Serum bactericidal activity values achieved after intravenous and oral therapy were similar. Response to therapy was evaluated separately in patients with or without osteomyelitis. In 30 patients with infections other than osteomyelitis, clinical cure was achieved in 27 (90 percent), and therapy failure occurred in three patients. In the 20 remaining patients with osteomyelitis, 15 (75 percent) had a satisfactory response, with apparent cure after a mean follow-up of 11 months, whereas five had therapeutical failure ( P. aeruginosa became resistant in four of them). Overall, no major adverse effects were encountered. Superinfection by a resistant P. aeruginosa was observed in three patients. Intravenous ciprofloxacin is an effective and safe agent for the therapy of severe infections caused by susceptible organisms.

Pharmacokinetics of scopolamine during caesarean section: relationship between serum concentration and effect.

The pharmacokinetics (radioreceptor assay, RRA) and some of the clinical effects of the anticholinergic agent, scopolamine, were studied in 16 parturients during caesarean section. Following a single 0.005 mg/kg intramuscular injection (deltoid muscle), a very fast rate of absorption was found with mean peak serum concentrations occurring after only 10 min (n = 6). Due to severe bradycardia, 0.5 mg of atropine i.v. had to be given in addition to the i.m. scopolamine treatment to one parturient. The RRA measured the total concentration produced by the two anticholinergic agents in both serum and urine. There was a fundamental difference in the diffusion of scopolamine through the placenta and the blood-lumbar (CSF-barrier (n = 15). There was significant drug penetration in the foeto-placental unit, indicating an efficient drug transfer to the child, but there were measurable levels of the drug in the lumbar CSF in only three cases. The apparent elimination phase half-life of scopolamine in serum was only around 1 h. The urinary excretion of scopolamine and/or its antimuscarinic metabolites lasted only for 6 h (2.63 +/- 1.14% of the dose). The onset of the clinical effects of scopolamine appeared to be delayed, but long-lasting in contrast to the rapid absorption and quick disappearance from the serum. Both the heart rate changes, sedative and antisialogogue effects and serum concentrations did not show any correlation. There appears to be a surprisingly great difference between the pharmacokinetic parameters and the clinical effects of scopolamine.

Intramuscular atropine in elderly people: pharmacokinetic studies using the radioreceptor assay and some pharmacodynamic responses.

The pharmacokinetics (radioreceptor assay, RRA) and some clinical effects of atropine were studied in 7 elderly gynaecological surgery patients. The RRA measures only the pharmacologically active isomer of atropine, 1-hyoscyamine. Following a single 0.01 mg/kg intramuscular (M. deltoideus) injection, a very fast rate of absorption was found with mean peak serum concentration occurring after only 13 min. The reason for this could be either a preferential tissue uptake of the 1-form or the injection site or both. The elimination half-life was 2.27 hr. Only 23.1% of the given drug was excreted in urine in 24 hr as a pharmacologically active form. The clinical effects (heart rate rise, subjective sedation and antisialogogue effect) were seen after only 30 min. This somewhat faster appearance of clinical effects than in previous studies can be due to the injection site. The sedative effect of the drug is clear and long lasting in elderly people.

Hemodynamic and Electrophysiologic Effects of Disopyramide Enantiomers in a Canine Blood Superfusion Model

The use of disopyramide is often limited because of adverse hemodynamic or electrophysiologic side effects. We compared the S(+) and R(-) enantiomers of disopyramide to the clinically used racemic mixture in a canine blood superfusion model. Eighteen support animals (group I) provided extracorporeal blood superfusion of isolated canine cardiac Purkinje fibers. Following administration of 2 mg/kg disopyramide intravenously (i.v.) [S(+), R(-), or racemic] hemodynamic and electrocardiographic parameters were temporally assessed in the support animals while simultaneous cellular electrophysiologic effects were recorded from the blood-superfused Purkinje fibers. An additional 13 animals (group II) underwent extended hemodynamic and pharmacokinetic analysis without the external atrioventricular (AV) shunt required for blood superfusion. Mean peak serum concentrations of racemic disopyramide and its enantiomers were similar (2.7 to 3.1 mg/L), but clearance was stereo-specific [half-life (t1/2) of 1.99 h for S(+) vs. 2.79 h for R(-) disopyramide]. Left ventricular (LV) function was impaired following drug administration, irrespective of optical rotation (cardiac output decreased by 20.8%, LV dP/dtmax decreased by 22.4%). Depression of phase 0 Vmax of the Purkinje fiber action potential was also nonstereo-dependent. S(+) disopyramide prolonged the QTC interval by 11.5% and increased terminal action potential duration (APD75) and effective refractory period (ERP) by 21.2 and 19.0%, respectively. R(-) disopyramide slightly increased the QTC interval (+2.3%) but decreased APD75 and ERP by 8.9 and 6.8%, respectively. The effect of racemic disopyramide on repolarization indexes was intermediate to that of its enantiomers. These data support nonstereodependent depression of both myocardial contractility and sodium channel conductance by disopyramide. Changes in APD and refractoriness were dependent on stereochemical configuration.

High-dose melphalan, misonidazole, and autologous bone marrow transplantation for the treatment of metastatic colorectal carcinoma. A phase I study.

To augment the antitumor effect of high-dose melphalan and determine pharmacokinetics we conducted a phase I trial of escalating doses of high-dose IV melphalan with the chemosensitizer misonidazole for patients with advanced colorectal carcinoma. Fourteen patients with modified Dukes D adenocarcinoma of the colorectum were treated with a single course of melphalan (40-60 mg/m2 i.v. bolus q.d. X 3 days) and misonidazole (1-3 g/m2 p.o. q.d. X 3 days) followed by autologous bone marrow transplantation. Toxicity consisted of severe myelosuppression, moderate nausea and vomiting, and mild mucositis and diarrhea. One patient developed unexplained renal tubular acidosis, and a diffuse encephalopathy occurred in another patient. Three patients died within the first 30 days after the start of treatment, two due to tumor progression and one due to sepsis and disseminated intravascular coagulation-induced intracerebral hemorrhage. Six of 14 patients achieved a partial response, and the median response duration was 4 months (range 3-10 months). Analysis of misonidazole serum concentrations showed similar pharmacokinetics to those previously reported, suggesting no significant drug interaction with intravenous melphalan. Mean peak serum concentrations ranged from 81.8 micrograms/ml to 115.2 micrograms/ml at the second and third misonidazole dose levels, which approximate those known to provide effective chemosensitization with melphalan in animal models. In this phase I study, we showed that maximally tolerated doses of intravenous melphalan can safely be combined with oral misonidazole. In view of the large volumes of oral misonidazole required at the highest dose level, subsequent studies to determine the maximally tolerated dose of misonidazole should employ the intravenous form.

The penetration of aztreonam, a monobactam antibiotic, into intra-abdominal abscesses.

We have studied the penetration of aztreonam into pus with a low mortality intra-abdominal abscess model in the Wistar rat. The mean peak serum concentration (standard error) of aztreonam was 74.6 +/- 9.88 mg/l at 30 min falling to 2.31 +/- 1.28 mg/l at 8 h. The mean concentration in pus was 17.04 +/- 2.01 mg/l at 2 h and was 14.47 +/- 2.23 mg/l at 8 h. These concentrations are in excess of the MICs of most Gram-negative aerobic bacilli commonly isolated from intra-abdominal abscesses.

Pharmacokinetics of diltiazem in patients with liver cirrhosis.

The pharmacokinetics of diltiazem (DTZ) was investigated in seven control subjects with normal liver function and in seven patients with liver cirrhosis. After long-term oral administration of diltiazem, 30 or 60 mg thrice daily, serum levels of DTZ and its active metabolites, deacetyl DTZ (DAD) and N-demethyl DTZ (DMD), were determined by high performance liquid chromatography. The mean peak serum concentrations (nmol/L) in control patients were 280 for DTZ, 58 for DAD and 101 for DMD. In cirrhotic patients, the serum DTZ tended to increase and the DAD increased (p less than 0.05), while the DMD decreased (p less than 0.05) compared with that of the control (335 for DTZ, 133 for DAD and 77 for DMD, nmol/L). Pharmacokinetic analysis using a one-compartment model revealed no change in the absorption, but a decrease in the elimination for cirrhotic patients (t 1/2; 5.3 to 7.2 h, p less than 0.1). The elimination rate constant correlated with some biochemical indices for hepatocyte function. These results may be explained by the impaired oxidative metabolism of diltiazem in liver cirrhosis.

Pharmacokinetics of cefonicid in children

The pharmacokinetics of cefonicid was studied in 17 children requiring antibiotic treatment for respiratory or urinary tract infections. After informed consent had been obtained from the parents, a single dose of cefonicid 50 mg/kg/body weight was given by intramuscular injection. The mean peak serum concentration of 212.63 micrograms/ml was reached at 1.00 h, as absorption occurred at a very fast rate with a mean constant of 3.24 h-1. Mean values for half-life, apparent volume of distribution (Vz), total body clearance (CL), and renal clearance (CLR) were 3.24 h, 0.21 l.kg-1, 16.67 ml.min-1 and 13.60 ml.min-1 respectively. There was an inverse relationship between age and Vz, whereas CL and CLR were positively correlated with age. Cefonicid concentrations in urine were many times higher than the MICs of susceptible strains of bacteria. The study demonstrated that i.m. cefonicid 50 mg.kg-1 gave serum concentrations well within the therapeutic range for susceptible bacteria, and that its pharmacokinetic properties allow single daily doses to be used to treat infections in children.

Systemic Absorption of Tetracycline and Lidocaine following Intrapleural Instillation

Seven patients with symptomatic pleural effusions (six) and recurrent pneumothorax (one) underwent attempted pleurodesis using tetracycline. Lidocaine (150 mg), followed immediately by tetracycline (20 mg/kg), was instilled into the pleural space through a chest tube. Venous blood was obtained at 0, 15, 30, 60, and 120 minutes following instillation in order to determine concentrations of lidocaine and tetracycline. The mean peak serum concentration of lidocaine was 1.3 mu/ml +/- 0.4 microgram/ml (mean +/- SE) (range, 0.3 microgram/ml to 3.2 microgram/ml), and the mean time to peak serum concentration of lidocaine was 86 +/- 13 minutes. The mean peak serum concentration of tetracycline was 3.6 microgram/ml +/- 0.9 microgram/ml (range, 1.0 microgram/ml to 5.0 micrograms/ml), and the mean time to peak serum concentration of tetracycline was 96 +/- 16 minutes. Therapeutic serum concentrations of lidocaine were found in four of the seven patients and therapeutic serum levels of tetracycline in four of five patients. With systemic absorption of lidocaine and tetracycline following intrapleural instillation, patients are at risk for potential toxic effects. If lidocaine is used in a dosage of less than 3 mg/kg, toxic levels of the drug are unlikely to occur. Furthermore, use of tetracycline or lidocaine in pleurodesis is contraindicated in patients with known sensitivity to the drugs.

Pharmacokinetics and tissue penetration of cefpirome, a new cephalosporin.

The pharmacokinetics and tissue penetration (as measured by a blister fluid model) of cefpirome were studied in six male volunteers following a 1 g intravenous dose. A mean peak serum concentration (at 5 min) of 97.4 mg/l was followed by rapid distribution into an apparent volume of 21.3 1. The serum elimination half-life was 2.3 h. Cefpirome penetrated rapidly into inflammatory fluid with a mean peak concentration of 39.2 mg/l at 1.9 h. The mean inflammatory fluid elimination half-life was 2.5 h. The availability of the drug in inflammatory fluid was high with a mean per cent penetration of 123%. The plasma and renal clearances were 109.5 and 82.1 ml/min respectively. Twenty-four hour urinary recovery was 75.5% of the administered dose. This study suggests that a twice daily dosage may be sufficient to treat tissue infections with susceptible pathogens.

In vitro activity of desacetylcefotaxime and the interaction with its parent compound, cefotaxime.

Antibacterial activities of cefotaxime and its major metabolite, desacetylcefotaxime, against 178 strains (of 10 species) were assessed in terms of minimum inhibitory concentrations (MIC50 and MIC80), and were compared with those of cefoperazone and ceftazidime. The activity of desacetylcefotaxime was several times less than that of cefotaxime against almost all of the species tested. Against Staphylococcus aureus, Morganella morganii, Enterobacter cloacae and Pseudomonas aeruginosa, the MIC80 values of desacetylcefotaxime were higher than those of cefoperazone and ceftazidime. The antibacterial potency of desacetylcefotaxime against Klebsiella pneumoniae and Pseudomonas cepacia was superior to that of cefoperazone and ceftazidime, and comparable with the activities of the latter compounds against the other 4 Gram-negative species. Partial synergy was demonstrated in the activity of cefotaxime and desacetylcefotaxime against most of the strains examined. Antagonism was observed in activity against 2 of 18 strains of M. morganii. In general, desacetylcefotaxime enhances the potency of its parent compound, cefotaxime, when they coexist. Intravenous infusion of cefotaxime 1 g over a period of 1 hour resulted in mean peak serum concentrations of 48.5 mg/L of cefotaxime and 6.5 mg/L of desacetylcefotaxime at the end of the infusion. The mean elimination half-life in beta-phase of cefotaxime was 0.8 hour and that of desacetylcefotaxime was 2 hours.