Pharmacokinetics of vancomycin in patients undergoing continuous ambulatory peritoneal dialysis.

The pharmacokinetics of vancomycin were studied in four patients on continuous ambulatory peritoneal dialysis. After a single intravenous infusion of 10 mg/kg of total body weight, multiple blood, urine, and dialysate samples were collected during a 72-h evaluation period. The steady-state volume of distribution was 0.73 +/- 0.07 (mean +/- standard deviation) liters/kg with a beta half-life of 90.2 +/- 24.2 h. The continuous ambulatory peritoneal dialysis clearance of vancomycin was 1.35 +/- 0.35 ml/min, and the serum clearance was 6.4 +/- 1.1 ml/min. Peritoneal dialysate concentrations of vancomycin were rapidly attained after the intravenous infusion and averaged 2.2 +/- 0.7 mg/liter throughout the 72-h observation period. A loading dose of 23 mg/kg followed by a maintenance dose of 17 mg/kg every 7 days should attain and maintain therapeutic serum and dialysate concentrations. More frequent dosing may be necessary for less susceptible organisms.     

Peritoneal transport of cefonicid

The pharmacokinetic characteristics of cefonicid, a highly protein-bound expanded-spectrum cephalosporin, were examined in six noninfected, clinically stable patients undergoing continuous ambulatory peritoneal dialysis. After a 1.0-g intravenous dose of cefonicid, the mean concentrations in serum were 105 +/- 25 and 35.6 +/- 14.4 micrograms/ml at 3 and 72 h, respectively. Despite a prolonged half-life in serum of 49.7 +/- 18 h, the penetration into peritoneal fluid was low. The average concentration in dialysate over the 72-h study period was 2.7 micrograms/ml. The serum clearance was 2.6 +/- 1.0 ml/min, and the distribution volume was 0.14 +/- 0.02 liter/kg. Dosage recommendations and clinical considerations for cefonicid use in continuous ambulatory peritoneal dialysis patients are discussed.     

Pharmacokinetics of single dose intravenous vancomycin in CAPD peritonitis

The pharmacokinetics of single dose intravenous vancomycin (25 mg/kg) were studied in six patients with peritonitis complicating continuous ambulatory peritoneal dialysis. The volume of distribution after equilibration was 1.1 +/- 0.1 l/kg (mean +/- standard error) with a serum elimination half-life of 115 +/- 6 h. The peritoneal clearance was 1.4 +/- 0.5 ml/min and the serum clearance was 7.2 +/- 0.3 ml/min. Mean peak serum levels of 56.8 +/- 4.7 mg/l were detected. Initial mean overnight dialysate level was 12.3 +/- 0.8 mg/l. Vancomycin dialysate levels of 8 mg/l were achieved for a mean of 3.0 days and levels of 4 mg/l for a mean of 6.2 days. Single dose intravenous vancomycin may, therefore, have therapeutic value in selected patients.     

Pharmacokinetics and metabolism of intravenous and oral fleroxacin in subjects with normal and impaired renal function and in patients on continuous ambulatory peritoneal dialysis.

The pharmacokinetics of fleroxacin, including the formation of N-demethyl and N-oxide fleroxacin after the administration of single intravenous (100-mg) and oral (400-mg) doses, was investigated in 26 subjects with various levels of renal function, including 7 patients on continuous ambulatory peritoneal dialysis. Fleroxacin was well tolerated by all subjects. The volume of distribution, systemic availability, and peak concentration after the administration of oral fleroxacin were independent of the glomerular filtration rate. As a consequence of a declining renal clearance but not nonrenal clearance, the total body clearance of fleroxacin declined with decreasing glomerular filtration rate from 1.41 +/- 0.23 ml/min per kg in subjects with normal renal function to 0.58 +/- 0.13 ml/min per kg in patients with end-stage renal disease (r = 0.84, P less than 0.001). The analysis revealed that the N-oxide metabolite exhibited formation-limited kinetics and the N-demethyl metabolite exhibited elimination-limited kinetics. The areas under the curve of both metabolites increased with declining renal function. In patients on continuous ambulatory peritoneal dialysis the mean dialysate/plasma concentration ratio of fleroxacin increased from 0.52 +/- 0.11 to 0.71 +/- 0.13 (P less than 0.001) with increasing dwell time, resulting in a 7.8 +/- 3.6% recovery of unchanged fleroxacin in peritoneal dialysate. In conclusion, (i) a 50% reduction of the maintenance dose is recommended in patients with a renal function below 20 to 30 ml/min per 1.73 m2, and (ii) therapeutic concentrations of fleroxacin in the peritoneal dialysate should be achievable after oral administration in patients on continuous ambulatory peritoneal dialysis.     

Pharmacokinetics of metronidazole in patients undergoing continuous ambulatory peritoneal dialysis

The pharmacokinetics of metronidazole, its biologically active alcohol metabolite, and its inactive acid metabolite were studied in five noninfected patients undergoing continuous ambulatory peritoneal dialysis and five patients undergoing hemodialysis. The latter were studied on off-dialysis days as a control group. Peritoneal dialysis caused insignificant changes in the apparent volume of distribution, elimination half-life, and total body clearance of metronidazole. Peritoneal dialysis clearance (4.49 +/- 0.88 ml/kg per h [mean +/- standard deviation]) accounted for only 8.9% of total body clearance (50.17 +/- 18.64 ml/kg per h). Analysis of the 24-h area under the serum concentration versus time curves and peritoneal dialysis clearance data for the two metabolites suggested a similar insignificant effect of peritoneal dialysis on their elimination. Metronidazole dialysate concentrations in the first 6-h exchange ranged from 7.6 to 11.7 micrograms/ml. This would suggest that cumulative penetration of metronidazole from the systemic circulation into the peritoneal cavity with dosing every 8 h should lead to adequate concentrations for the treatment of anaerobic peritonitis. For the treatment of systemic anaerobic infections, it would appear at present that metronidazole dosage adjustments are not necessary in patients undergoing continuous ambulatory peritoneal dialysis. The potential for metabolite accumulation was noted in this study. If further studies confirm that excessive serum metabolite concentrations are toxic, dosage reduction in this group of patients may be warranted.     

Pharmacokinetics of ceftizoxime in patients undergoing continuous ambulatory peritoneal dialysis.

The pharmacokinetics of ceftizoxime were studied in 12 patients on continuous ambulatory peritoneal dialysis. After a 3-g intravenous dose, the steady-state volume of distribution was 0.23 +/- 0.05 liter kg-1, with an elimination half-life of 9.7 +/- 5.1 h. The peritoneal clearance of ceftizoxime (2.8 +/- 0.7 ml min-1) contributed modestly to the overall serum clearance of the drug (17.1 +/- 7.4 ml min-1) and was greater than the renal clearance (0.8 +/- 0.8 ml min-1). The peritoneal concentration rose to 91 +/- 29 micrograms ml-1 at 6 h, which was 0.61 +/- 0.17 of the serum concentration. A 3-g intravenous dose of ceftizoxime given every 48 h would result in adequate activity against most susceptible organisms, but more frequent dosing may be necessary for less susceptible organisms.     

Absorption of ciprofloxacin in patients with diabetic gastroparesis.

The purpose of this study was to assess the pharmacokinetic profile of ciprofloxacin in 12 patients with diabetic gastroparesis. Patients received both a single 500-mg oral (p.o.) dose and a single 400-mg intravenous (i.v.) dose of ciprofloxacin separated by a 1-week washout period. Pharmacokinetic parameters (means +/- standard deviations) for the p.o. and i.v. doses were as follows: areas under the concentration-time curve from 0 h to infinity, 9.74 +/- 2.59 and 11.78 +/- 3.18 micrograms.h/ml, respectively; maximum concentrations of drug in serum, 2.13 +/- 0.67 and 4.21 +/- 1.07 micrograms/ml, respectively; and half-lives, 4.03 +/- 0.58 and 4.20 +/- 0.58 h, respectively. The ratio of the areas under the concentration-time curves from 0 h to infinity for the p.o. and i.v. doses was 0.84, with a 90% confidence interval of 0.68 to 0.98; the mean absolute bioavailability was calculated to be 67% (range, 43 to 82%). From these data it appears that ciprofloxacin is adequately absorbed in patients with diabetic gastroparesis.     

Comparison of steady-state pharmacokinetics of two dosage regimens of vancomycin in normal volunteers.

A pharmacokinetic comparison of the two recommended dosages of vancomycin given as multiple doses has not been previously performed. Eleven adult subjects with normal renal function randomly received 500 mg every 6 h (five doses) and, later, 1,000 mg every 12 h (three doses). Each dose was infused over 1 h, and regimens were separated by 1 week. Compared with the two-compartment fit, a three-compartment fit significantly reduced the residual weighted sums of squares. Accumulation occurred for both regimens after repeated dosing and was independent of dose. At steady state, concentrations in serum at 1 h showed little variation for the 1,000- or the 500-mg dose regimen (33.7 +/- 3.8 versus 22.6 +/- 3.2 micrograms/ml); trough concentrations were 7.9 +/- 1.7 versus 11.2 +/- 2.2 micrograms/ml, respectively. With the 1,000-mg dose, the terminal half-life was 7.7 +/- 1.8 h, steady-state area under the curve for the dose interval was 227 +/- 28.3 micrograms X h/ml, and total body clearance was 86.1 +/- 8.9 ml/min per 1.73 m2. The red-man syndrome occurred in 9 of 11 volunteers who received 1,000-mg doses and in none of those who received 500-mg doses. We concluded that vancomycin disposition in healthy adults with normal renal function is best described by a three-compartment model, there is relatively little variation in vancomycin disposition in normal volunteers, significant accumulation occurs with multiple dosing, it is inappropriate to use the same therapeutic window for both regimens, and the pharmacokinetics of vancomycin justify a 12-h dose interval; however, a 1-g dose is associated with a significantly greater incidence of the red-man syndrome.     

Hepatobiliary kinetics and excretion of ciprofloxacin.

The biliary excretion and metabolism of ciprofloxacin was studied in 25 hospitalized patients: 19 undergoing routine cholecystectomy and 6 with indwelling biliary drainage catheters. An intravenous dose of 200 mg of ciprofloxacin given 2.5 to 3.0 h prior to cholecystectomy resulted in concentrations in common duct bile, gallbladder bile, and gallbladder wall of 5.69 +/- 4.8, 5.43 +/- 3.34, and 2.52 +/- 1.30 micrograms/g, respectively, all at least fourfold greater than simultaneous concentrations in serum. Ciprofloxacin concentrations in common duct bile exceeded peak concentrations in serum in all but two patients with common duct obstruction. Multiple preoperative doses of ciprofloxacin prior to cholecystectomy increased concentrations in gallbladder bile by eightfold. Six patients with indwelling biliary drainage catheters also received 200 mg of ciprofloxacin intravenously. Less than 1% of the administered dose was excreted in bile as unchanged ciprofloxacin, and there was extensive metabolism. However, peak ciprofloxacin concentrations of 2.83 +/- 0.76 micrograms/ml in serum produced peak concentrations of 10.69 +/- 5.30 micrograms/ml in bile within 1.5 h after infusion and maintained concentrations of at least 0.5 microgram/ml in common duct bile for over 12 h in all patients. It appears that ciprofloxacin concentrations in bile will exceed the MICs for most susceptible biliary pathogens for a period of at least 12 h after a 200-mg intravenous dose.     

Pharmacokinetics of intravenous and intraperitoneal cefotaxime in chronic ambulatory peritoneal dialysis

We investigated the kinetics of cefotaxime in eight subjects undergoing continuous ambulatory peritoneal dialysis (CAPD). A single 1 gm iv dose was injected and a 1 gm dose was given intraperitoneally in the CAPD fluid during a 4-hour dwell time. Cefotaxime and desacetylcefotaxime were assayed by HPLC. After intravenous injection the cefotaxime serum kinetic parameters were as follows: plasma t 1/2, 2.31 +/- 0.20 hours; volume of distribution, 0.35 +/- 0.04 L/kg; total plasma clearance, 118.7 +/- 12.3 ml/min; and peritoneal clearance, 6.7 +/- 1.3 ml/min. Dialysate cefotaxime concentrations rose rapidly, but only 5% of the dose was eliminated by the peritoneal route. After intraperitoneal instillation, cefotaxime appeared in the serum rapidly and the peak serum concentrations ranged from 9 to 20 micrograms/ml between 1 and 3 hours. The absorption of cefotaxime from peritoneal space was 58.7% +/- 5.4%. Data suggest that cefotaxime has bidirectional exchange characteristics through the peritoneal membrane. Instillation of cefotaxime in CAPD fluid may permit rapid absorption to achieve therapeutic serum concentrations.     

Ceftriaxone kinetics and cerebrospinal fluid penetration in infants and children with meningitis

20 patients (0.4-5.6 years old) receiving ceftriaxone for the treatment of bacterial meningitis were studied. Simultaneous serum and cerebrospinal fluid concentrations of ceftriaxone were determined by HPLC in 15 patients at 11.4-12.8 h after an intravenous loading dose of 75 mg/kg. Serum and cerebrospinal fluid concentrations ranged from 20.5 to 44.9 (31.3 +/- 7.8) and from 1.1 to 8.0 (3.7 +/- 1.8) micrograms/ml, respectively. Cerebrospinal fluid concentrations ranged from 3 to 25% (12 +/- 6%) of the simultaneous serum concentrations. In 6 patients, serum and cerebrospinal fluid concentrations were determined after maintenance doses of 50 mg/kg/12 h. Serum and cerebrospinal fluid concentrations ranged from 120 to 144 and 2.3-4.9 micrograms/ml at 1.8-5.5 h after the first maintenance dose in 2 patients; 74-139 and 5.7-7.9 micrograms/ml at 1.3-5.8 h after the second dose in 3 patients and was 101 and 4.1 micrograms/ml at 4 h after the 3rd dose in 1 patient. Multiple blood samples were collected after the loading dose in 5 patients and after 9-10 days of maintenance doses in 3 patients. Steady-state peak and trough serum concentrations ranged from 295 to 440 and 32.6-44.8 micrograms/ml, respectively. After the loading and maintenance dose at steady-state, total body clearance averaged 1.17 and 0.64 ml/min (p = 0.01); apparent volume of distribution averaged 0.37 and 0.26 l/kg (p greater than 0.05); and elimination half-life averaged 3.7 and 4.6 h (p = 0.01), respectively. These results suggest that (1) adequate cerebrospinal fluid concentrations of ceftriaxone can be achieved in patients with meningitis with the dosage regimen studied.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of single-dose oral ciprofloxacin in patients undergoing chronic ambulatory peritoneal dialysis.

The prevention and treatment of peritonitis in patients undergoing peritoneal dialysis is often complicated by several factors, including nephrotoxicity, requirement for hospitalization, parenteral antibiotic therapy, and infection caused by resistant microorganisms. Ciprofloxacin, a new carboxyquinolone derivative, may offer the advantages of oral administration, a broad spectrum of antibacterial activity, and safety for the management of these patients. The pharmacokinetics of ciprofloxacin in serum and peritoneal fluid of eight adult patients undergoing chronic ambulatory peritoneal dialysis (CAPD) were investigated. Each patient ingested a single 750-mg dose of ciprofloxacin, and drug concentrations were measured by high-pressure liquid chromatography in serum and peritoneal fluid for 48 h after the dose. Serum concentrations reached a mean peak of 3.6 micrograms/ml 1 to 2 h after the oral dose. The mean terminal serum half-life was 16.8 h, and the mean peritoneal fluid/serum concentration ratio was 0.64. The mean peak ciprofloxacin concentration in peritoneal fluid was 1.3 micrograms/ml, and the bioactivity of the drug in peritoneal fluid was confirmed. These data indicated that therapeutic concentrations of ciprofloxacin against bacterial pathogens commonly associated with peritonitis in CAPD patients may be achievable in the peritoneal fluid after oral administration to patients undergoing CAPD. In addition, the pharmacokinetic data provide guidelines for further clinical studies of oral ciprofloxacin in CAPD patients.     

In vitro activity and human pharmacokinetics of teicoplanin.

The in vitro activity of teicoplanin, a new antibiotic related to vancomycin, was determined against 456 gram-positive cocci. The activity of teicoplanin in comparison with that of vancomycin was similar against staphylococci but 4 to 40 times higher against enterococci and beta-hemolytic and viridans streptococci. The single-dose pharmacokinetics of teicoplanin were studied in six healthy volunteers after administration of 3 and 6 mg/kg intravenously and of 3 mg/kg intramuscularly. The kinetic parameters after both intravenous doses were very similar. The curves for concentration in plasma for the 3- and 6-mg/kg intravenous doses showed a triexponential decline with elimination half-lives of 47.3 and 44.1 h, respectively. The percentages of the doses recovered in urine (0 to 102 h) were 43.2 and 44.1%, respectively. The areas under the plasma curves were dose related: 256.5 and 520.9 micrograms/h per ml, respectively. The bioavailability of teicoplanin after injection of 3 mg/kg intramuscularly was 90%, and the peak level was 7.1 micrograms/ml. The mean levels in plasma 24 h after the 3-mg/kg doses were 2.1 and 2.3 micrograms/ml, respectively, and the mean level in plasma 24 h after the 6-mg/kg intravenous dose was 4.2 micrograms/ml.     

Cerebrospinal fluid penetration of imipenem and cilastatin (primaxin) in children with central nervous system infections.

Cerebrospinal fluid (CSF) penetration of imipenem-cilastatin was evaluated in 20 children (aged 4 months to 11 years) with central nervous system infections. A total of 10 children received a single 25-mg/kg intravenous dose, and 10 received three 25-mg/kg intravenous doses at 6-h intervals. Blood and CSF were obtained 1.5 to 2.5 h after the last dose during the early (days 1 to 3) and the late (days 7 to 10) stages of infection. Imipenem concentrations after single-dose infusion in serum and CSF during the early phase of treatment (8.59 +/- 0.95 and 1.36 +/- 0.32 micrograms/ml, respectively) were similar to those during the late phase (9.96 +/- 2.36 and 2.08 +/- 1.14 micrograms/ml, respectively). Concentrations of imipenem in serum and CSF after multiple-dose infusion during the early phase (11.97 +/- 2.03 and 1.87 +/- 0.29 micrograms/ml, respectively) were similar to those during the late phase (9.57 +/- 1.76 and 1.22 +/- 0.11 micrograms/ml, respectively). There were no significant differences in the serum or CSF imipenem concentrations between the single- and multiple-dose groups during the early or late treatment stages. Cilastatin concentrations in serum and CSF were similar in all groups with the exception of the multiple-dose, early- versus late-phase evaluation of CSF cilastatin concentration. There was no correlation between age or absolute CSF neutrophil count and the serum or CSF concentrations of imipenem or cilastatin. We found a mean CSF penetration of 15 to 27% for imipenem and 16 to 66% for cilastatin in children. These findings suggest that imipenem-cilastatin sufficiently penetrates into CSF in children to warrant further investigation of this compound in pediatric central nervous system infections.     

Moxalactam kinetics during continuous ambulatory peritoneal dialysis after intraperitoneal administration.

Moxalactam kinetics during continuous ambulatory peritoneal dialysis (CAPD) was followed in eight patients after a single intraperitoneal dose of 1 g. Approximately 60% of the dose was absorbed after a dwell time of 4 h. Dialysis solutions were exchanged at 4-h intervals with an overnight dwell of 8 h. The mean (+/- standard deviation) elimination half-life was 13.2 +/- 2.9 h, and the mean apparent volume of distribution was 0.22 +/- 0.08 liters/kg. Mean total clearance was 11.5 +/- 2.4 ml/min, with a mean dialysis clearance of 2.3 +/- 0.5 ml/min. The maximum concentration in plasma ranged from 24.5 to 54.1 micrograms/ml. Moxalactam concentrations in the peritoneal dialysis fluid were above 80 micrograms/ml during the first exchange and above 2 micrograms/ml for a further three exchanges. A suggested intraperitoneal dose regimen for patients undergoing CAPD is 1 g initially, followed by 15 to 25% of the recommended dose for normal patients given at the same time intervals, or 30 to 50% of the recommended dose at twice the usual intervals. Moxalactam is suggested for initial treatment of peritonitis in CAPD patients who do not have ready access to the antibiotic of choice.     

Use of intravenous rifampin in neonates with persistent staphylococcal bacteremia.

Ten neonates with persistent staphylococcal bacteremia (positive blood cultures for > or = 5 days despite appropriate antibiotic therapy) received intravenous (i.v.) rifampin in combination with vancomycin with or without aminoglycoside. Their mean birth weight and length of gestation were 900 g and 27 weeks, respectively. Their ages at the time of infection ranged from 6 to 64 days (mean, 26 days). The staphylococcal isolates were methicillin-resistant Staphylococcus aureus (five isolates), methicillin-susceptible S. aureus (two isolates), and coagulase-negative staphylococci (three isolates). The mean number of bacteremia days prior to administration of i.v. rifampin was 8.3 (range, 5 to 15 days), despite a mean peak vancomycin concentration of 33 micrograms/ml. The dosing of rifampin varied from 2.5 to 10 mg/kg of body weight every 12 h. The mean duration of the rifampin course was 9.7 days (range, 3 to 16 days). Of the 10 neonates, 8 (80%) had sterile blood cultures within 24 h, 1 (10%) had a sterile blood culture within 48 h, and 1 (10%) had a sterile blood culture within 5 days of being placed on i.v. rifampin. No adverse effects were noted in this small group of infants. Seven of the 10 neonates survived; three died from unrelated complications. The MIC ranges of amikacin, vancomycin, and rifampin for the isolates were 2.0 to 16, 0.5 to 2.0, and 0.0013 to 0.04 micrograms/ml, respectively. We also studied eight infants, with a mean age of 23 days, who were receiving i.v. or oral rifampin at a dose of 10 mg/kg/day. For i.v. administration, the peak serum concentration of rifampin (mean +/- standard deviation) was 4.02 +/- 1.22 microgram/ml. The mean trough level at 12 h postifution was 1.11 +/- 0.48 micrograms/ml. For oral administration, the concentrations of rifampin in serum ranged from 0.59 to 2.86 micrograms/ml (mean, 1.86 +/- 0.96 microgram/ml) at 2 h postingestion, increasing to a peak concentration of 2.8 micrograms/ml at 8 h postingestion. The mean 12-h postingestion level was 0.77 +/- 0.03 microgram/ml. From the study of this limited series of neonates, rifampin appears to be a safe and effective addition to therapy when staphylococcal bacteremia is persistent despite vancomycin treatment.     

Moxalactam epimer disposition in patients undergoing continuous ambulatory peritoneal dialysis

The kinetics of the epimers of moxalactam (R-MOX, S-MOX) were investigated in patients without infections who were receiving continuous ambulatory peritoneal dialysis after both intravenous and intraperitoneal injections of moxalactam. R-MOX and S-MOX were well absorbed from the peritoneal cavity, with mean systemic availability of 0.71 +/- 0.18 and 0.79 +/- 0.18, respectively. After intravenous MOX, serum clearance was 10.2 +/- 3.4 (R-MOX) and 10.9 +/- 3.2 (S-MOX) ml/hr/kg. Net time-averaged peritoneal dialysis clearance of both epimers was minimal, about 10% of serum clearance. Serum and dialysate MOX concentrations were above the minimum inhibitory concentrations for susceptible bacteria for 24 hours after a 2.0 or 1.0 gm intravenous or intraperitoneal dose. Gastrointestinal side effects occurred after a 2.0 gm dose (both intravenous and intraperitoneal) but not after a 1.0 gm dose. There were no significant differences in the kinetics of R-MOX and S-MOX. A single 1.0 gm ip dose leads to serum and dialysate MOX concentrations above the minimum inhibitory concentration for susceptible pathogens for 24 hours.     

Disposition of cefotaxime and desacetyl cefotaxime during continuous ambulatory peritoneal dialysis.

The disposition of cefotaxime (CTX) and desacetyl cefotaxime (DAC) was studied in eight noninfected patients on continuous ambulatory peritoneal dialysis. Each patient received a single intravenous (i.v.) infusion and an intraperitoneal (i.p.) instillation of 2 g of CTX. Multiple blood and dialysate samples were collected during the 72-h period after drug administration. The half-life, steady-state volume of distribution, and total body clearance of CTX following i.v. administration were 2.2 +/- 1.0 h (mean +/- standard deviation), 0.17 +/- 0.03 liters/kg, and 81.0 +/- 31.0 ml/min, respectively. No significant differences were observed in these parameters after i.p. administration. The continuous ambulatory peritoneal dialysis clearances of CTX and DAC were 1.82 +/- 0.43 and 2.84 +/- 0.70 ml/min, respectively, after i.v. administration. The bioavailability of CTX after i.p. instillation was 74.6 +/- 21.3%. Peak peritoneal dialysate CTX and DAC concentrations of 264.3 and 25.8 mg/liter, respectively, were observed after i.p. dosing. Administration (i.v.) of 2 g every 12 h or i.p. instillation of 2 g every 24 h may be used for the treatment of i.p. infections with highly susceptible organisms (MIC less than 1.0 microgram/ml).     

Effect of pancreatitis on ampicillin excretion in pancreatic fluids of dogs.

Pancreatic excretion of ampicillin was evaluated in normal dogs and in dogs with induced pancreatis. A 100-mg/kg ampicillin dose administered intravenously induced mean peak serum levels of 100 micrograms/ml, and a 200-mg/kg intravenous dose induced a mean peak serum level of 273 microgram/ml. Ampicillin serum levels did not differ between the group of normal dogs and those with pancreatitis. In normal dogs, the peak pancreatic fluid ampicillin concentration after the 100-mg/kg dose was 0.4 microgram/ml, and that after the 200-mg/kg dose was 2.7 micrograms/ml. In dogs with pancreatitis, the mean peak ampicillin concentration in the pancreatic fluid after the 100 mg/kg dose was 19 micrograms/ml, and that after the 200-mg/kg dose was 38.5 micrograms/ml. Pancreatic fluid ampicillin concentrations were therapeutic in dogs with pancreatitis and subtherapeutic in normal dogs.     

Pharmacokinetics and cerebrospinal fluid (CSF) concentrations of vancomycin in pediatric patients undergoing CSF shunt placement

Staphylococcus epidermidis has been established as the common pathogen causing cerebrospinal fluid shunt infections. In addition, clinical isolates of S. epidermidis from infected shunts are typically resistant to methicillin. Vancomycin is often used for neurosurgical prophylaxis due to its excellent in vitro activity against methicillin-resistant staphylococci. Limited data are available about the pharmacokinetics and cerebrospinal fluid concentrations of vancomycin in pediatric patients intraoperatively. The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal fluid concentrations of vancomycin. Eight patients (mean age 8.3 +/- 7.0 years) received three doses of intravenous vancomycin, 15 mg/kg every 6 h. The first dose was administered 1 h prior to surgery. Blood samples were collected at 0, 0.5, 1, 2, 4, and 5 h after the end of the infusion. A cerebrospinal fluid sample was collected at the time of shunt insertion. Urine samples were collected over a 24-hour period. Vancomycin was measured with a fluorescence polarization immunoassay. The peak serum concentrations ranged from 15.6 to 33.7 micrograms/ml; cerebrospinal fluid concentrations ranged from less than 0.6 to 0.8 microgram/ml. The mean total clearance, renal clearance, apparent volume of distribution, and elimination half-life were 0.11 +/- 0.05 l/h/kg, 0.07 +/- 0.02 l/h/kg, 0.54 +/- 0.15 l/kg, and 4.8 +/- 4.0 h, respectively. Approximately 70% of total vancomycin dose was excreted in the urine. A 2- to 5-fold variation in total clearance and a 2.5-fold variability in renal clearance were observed. Low cerebrospinal fluid concentrations of vancomycin were present at the time of shunt insertion in these pediatric patients.(ABSTRACT TRUNCATED AT 250 WORDS)