Pharmacokinetics of intravenous and intraperitoneal fosfomycin in continuous ambulatory peritoneal dialysis

Kinetics of fosfomycin were investigated in six patients undergoing continuous ambulatory peritoneal dialysis. Each subject received both an i.v. and an i.p. 1 g dose of fosfomycin with a one week washout between doses. Fosfomycin was assayed by a microbiological diffusion technique. After intravenous injection the fosfomycin serum kinetic parameters were as followed: elimination half-life (t1/2 beta) 38.4 +/- 8.7 h; volume of distribution 0.32 +/- 0.02 l/kg; total plasma clearance 7.0 +/- 1.4 ml/min and peritoneal clearance 3.2 +/- 0.2 ml/min. Dialyzate fosfomycin concentrations reached a maximum mean value of 32.2 +/- 2.8 micrograms/ml at 4 h post-injection and fosfomycin was detectable in dialyzate samples for up to 72 hours post-dosing. After intraperitoneal instillation, fosfomycin appeared in the serum rapidly and the mean peak plasma concentration was 36.2 +/- 2.8 micrograms/ml at the 4th h. The absorption rate (ka) was 0.580 +/- 0.039 h-1 and the absorption of fosfomycin from peritoneal space was 68.4 +/- 6.0%. These data suggest a bidirectional exchange through the peritoneal membrane. Intraperitoneal administration of 1 g either 48 h apart for anephric patients or 36 h apart for patients with residual renal function may achieve therapeutic serum concentrations.     

Pharmacokinetics of intraperitoneal cefotaxime treatment of peritonitis in patients on continuous ambulatory peritoneal dialysis

The pharmacokinetics of intraperitoneal cefotaxime as the sole therapy in patients on continuous ambulatory peritoneal dialysis with peritonitis have been examined. The mean plasma concentrations achieved following 1 h of peritoneal instillation of 500 mg of cefotaxime were 5.0 +/- 1.6 micrograms ml-1. The average plasma concentration over 24 h was 6.9 +/- 0.4 micrograms ml-1 and was no different from that found following a further 9-11 days of successful treatment of the peritonitis. However, the mean dialysate effluent concentration of cefotaxime was increased following the resolution of the peritonitis, 165 +/- 22.7 mg per cycle on day 10 or 12 compared with 50.4 +/- 7.3 mg per cycle on day 1, suggesting enhanced peritoneal cefotaxime absorption during acute peritonitis. Nevertheless, during both periods, adequate concentrations of cefotaxime were achieved in dialysate to treat local complications, but plasma levels may be inadequate to treat systemic complications due to Staphylococcus albus.     

Pharmacokinetics of oral cephradine in continuous ambulatory peritoneal dialysis patients

Parenteral cephalosporins are widely used to treat peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). Few data exist on oral antibiotics in treating this disease. This study examined the pharmacokinetics of oral cephradine in noninfected patients on CAPD. Assays for cephradine in dialysate and urine were performed by high-performance liquid chromatography. Following a 500-mg dose, the peak dialysate cephradine concentration was 8.7 +/- 1.4 micrograms/ml. The peak urinary concentration was 201 +/- 119 micrograms/ml. The maximum peritoneal clearance was 4.3 +/- 0.3 ml/min/1.73 m2. Dialysate cephradine concentrations were inadequate against Staphylococcus epidermidis and most gram-negative bacteria found in CAPD-associated peritonitis, but may be adequate for most strains of other gram-positive organisms causing this disease.     

Pharmacokinetics of intravenous ceftizoxime in patients on continuous ambulatory peritoneal dialysis

The pharmacokinetics of ceftizoxime (CZM) were determined in 16 non-infected CAPD patients. Patients received either 500 mg or 1000 mg CZM by i.v. bolus. The dialysate exchange volume was 2 l. Serum CZM concentrations at 10 min were 69.7 +/- 19.7 micrograms/ml (1000 mg dose) and 39.2 +/- 8.4 micrograms/ml (500 mg dose), and declined to 33.7 +/- 13.9 micrograms/ml and 16.9 +/- 3.2 micrograms/ml respectively at 360 min. Dialysate CZM levels at 10 and 360 min were 1.8 +/- 1.3 and 19.9 +/- 6.6 micrograms/ml respectively (1000 mg dose) and 1.4 +/- 0.9 and 12.6 +/- 3.5 micrograms/ml (500 mg dose). The half-time of CZM was 14.1 +/- 4.6 h. Peritoneal clearance of CZM was low and equilibrium was not achieved in 6 h. However peritoneal CZM concentrations were adequate within 1 h for the treatment of most organisms which cause CAPD-related peritonitis.     

Pharmacokinetics of calcitriol in continuous ambulatory and cycling peritoneal dialysis patients

Oral calcitriol is commonly used for the treatment of secondary hyperparathyroidism in patients undergoing long-term dialysis, but it has been suggested that intravenous (IV) or intraperitoneal (IP) administration enhances the therapeutic efficacy of the sterol. To examine potential mechanisms for this difference, the bioavailability of calcitriol was evaluated after single oral (PO), IV, and IP doses of 60 ng/kg in each of six adolescent patients with osteitis fibrosa undergoing continuous ambulatory peritoneal dialysis (CAPD) or continuous cycling peritoneal dialysis (CCPD). Serum calcitriol levels were 3.6 +/- 4.3, 8.2 +/- 7.5, and 2.5 +/- 3.0 pg/mL, respectively, before IV, PO, and IP doses of the sterol; these values increased to similar levels at 24 hours: 55.6 +/- 14.6 pg/mL after PO, 56.4 +/- 17.6 pg/mL after IV, and 53.8 +/- 20.1 pg/mL after IP. Serum calcitriol levels were higher 1, 3, and 6 hours after IV injections than after PO or IP doses; values thereafter did not differ among groups. The bioavailability of calcitriol, determined from the 24-hour area under the curve (AUC0-24) for the increase in serum calcitriol concentration above baseline values was 50% to 60% greater after IV, 2,340 +/- 523 pg.mL-1.h-1, than after PO, 1,442 +/- 467 pg.mL-1.h-1, or IP, 1,562 +/- 477 pg.mL-1.h1, dosages, P less than 0.05. These differences were due to higher values for AUC during the first 6 hours after calcitriol administration. Although IP calcitriol did not increase sterol bioavailability, radioisotope tracer studies indicated that 35% to 40% of the hormone adheres to plastic components of the peritoneal dialysate delivery system.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics and pharmacodynamics of captopril in patients undergoing continuous ambulatory peritoneal dialysis

Pharmacokinetics and pharmacodynamics of captopril were studied in 5 continuous ambulatory peritoneal dialysis (CAPD) patients (including 2 hypertensive patients) after single oral administration of 50 mg captopril. The pharmacokinetic parameters for plasma free unchanged captopril were time to maximal concentration 1.1 +/- 0.3 h, maximal plasma concentration 387 +/- 75 ng X ml-1, elimination half-life 1.0 +/- 0.3 h, and the area under the concentration-time curve 711 +/- 144 ng X h X ml-1. For plasma total captopril (the sum of free unchanged captopril and its disulfide compounds) the values were time to maximal concentration 3.5 +/- 0.6 h and maximal plasma concentration 2,777 +/- 429 ng X ml-1. Captopril was detected in the dialysis fluid in all CAPD patients. Blood pressures in the 2 hypertensive CAPD patients were lower at 24 h after than before captopril administration. These results suggest that captopril may be eliminated by CAPD. In addition, there is a possibility that the antihypertensive effects of captopril may be prolonged in hypertensive CAPD patients.     

Pharmacokinetics and pharmacodynamics of subcutaneous and intraperitoneal administration of recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis

The single-dose pharmacokinetics of 50 U/kg body weight of recombinant human erythropoietin (rHuEPO) given by either the subcutaneous (s.c.) or the intraperitoneal (i.p.) route were studied in 20 anemic patients maintained on continuous ambulatory peritoneal dialysis. Their baseline hemoglobin levels were less than 9 g/dl. The absorption of rHuEPO via the i.p. route was limited. The serum erythropoietin (EPO) level was only slightly elevated from a baseline value of 27 +/- 3 mU/l to a plateau of 36 +/- 4 mU/l at 12-24 hours. In comparison, after s.c. injection, a peak EPO level of 81 +/- 13 mU/l was obtained after 24 hours. The areas under the concentration-time curve from 0-24 hour were 803 +/- 67 and 1492 +/- 165 mU/l.h for the i.p. and s.c. group respectively (p less than 0.003). The same two groups of patients were then given rHuEPO by either the s.c. or the i.p. route over a period of 16 weeks. In the s.c. group, the hemoglobin increased significantly from 6.9 +/- 0.3 g/dl to 9.8 +/- 0.6 g/dl (p less than 0.004). The mean rHuEPO dosage was 84 +/- 9 U/kg body wt/week. In the i.p. group, despite relatively higher rHuEPO dosage (133 +/- 7 u/kg body wt/week), the hemoglobin level did not increase significantly (7.0 +/- 0.4 g/dl to 8.0 +/- 0.4 g/dl, p = 0.09). Subcutaneous administration of rHuEPO is effective and convenient for patients maintained on continuous ambulatory peritoneal dialysis.     

Pharmacokinetics of common antibiotics used in continuous ambulatory peritoneal dialysis

To establish therapeutic guidelines for the use of antibiotics in patients receiving continuous ambulatory peritoneal dialysis (CAPD), we studied the single-dose pharmacokinetics of cefazolin, tobramycin, and vancomycin given intravenously (IV) and intraperitoneally (IP) as well as cephalexin given orally. By the IV or oral route, the antibiotics exhibited half-lives similar to those described in nondialysed, functionally anephric patients. CAPD accounted for only a negligible fraction of the total body clearance when the drugs were given by the IV route. However, when given IP, the drugs were promptly absorbed and achieved therapeutic serum concentrations. The kinetic principle of superposition was applied to predict plasma concentrations after repetitive IP dosing. Therapeutic guidelines are provided.     

Potassium metabolism in continuous ambulatory peritoneal dialysis patients

Background: Hypokalemia is common and may have contributed to the poor clinical outcome in peritoneal dialysis (PD) patients. In this study, we made a detailed investigation on the potassium metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients and tried to find out the possible factors associated with the high prevalence of hypokalemia in PD patients. Methods: A cross-sectional survey in 243 clinically stable CAPD patients was made in our PD center in 2010. Patients were divided into four groups according to whether they were anuric or not and different dialysis regimens. Patients’ demographic data and data on potassium metabolism including dietary potassium intakes, residual renal potassium, and peritoneal dialysis potassium removal were collected. Results: The average potassium intake in our 243 PD patients was 32.1?±?11.1?mmol/day. The total potassium removal was significantly higher in non-anuric patients as compared to anuric patients (33.2?±?9.1 vs. 23.0?±?4.7?mmol/day for 3 exchanges per day and 35.2?±?8.9 vs. 28.6?±?6.3?mmol/day for 4 exchanges per day, respectively, p?p?p?p?R² linear?=?0.645, p?Conclusions: Our study suggested that if potassium intake was limited in PD patients, we should be aware of the risk of hypokalemia with high doses of PD when patients have good RRF. Our study also suggested that potassium removal in PD patients may not necessarily reflect potassium intake even if serum potassium is normal, the effect of ICW should be considered when evaluating potassium homeostasis.     

Aspergillus peritonitis in continuous ambulatory peritoneal dialysis patients

Aspergillus peritonitis is a rare and serious cause of peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients. We report 3 cases of aspergillus peritonitis in CAPD which were successfully treated by catheter removal and amphotericin. Two of the 3 patients returned temporarily to CAPD, but were subsequently transferred to hemodialysis because of membrane failure. A novel finding in 2 of the 3 cases was a positive Limulus amebocyte lysate test, despite negative bacterial cultures. We discuss the possible relevance of this finding to the diagnosis of aspergillus infections and emphasize the importance of early catheter removal for successful treatment of this condition.     

Influence of intraperitoneal dialyzate on blood pressure during continuous ambulatory peritoneal dialysis

Blood pressure (BP) of patients on continuous ambulatory peritoneal dialysis (CAPD) must be well controlled. The present study tests a clinical impression that BP recordings are higher with dialyzate within the peritoneal cavity than after it is drained out. 8 CAPD patients had systolic BP, diastolic BP and heart rate measured both with dialyzate in situ and after drainage. Paired t-tests showed systolic BP and diastolic BP but not heart rate to be significantly (P less than 0.05) higher with dialyzate in situ. To avoid a false impression of good BP control it is recommended patients on CAPD measure BP with dialyzate in situ.     

Treatment of gram-positive peritonitis with two intraperitoneal doses of vancomycin in continuous ambulatory peritoneal dialysis patients

Eight patients with end-stage renal failure on continuous ambulatory peritoneal dialysis (CAPD), who developed peritonitis, received an intraperitoneal dose of vancomycin (30 mg/kg body weight) with 6 h of peritoneal dwell and then resumed their routine CAPD schedule. Vancomycin concentration in serum, peritoneal dialysate (PD) from an overnight dwell and 1, 2 and 3 h after a new exchange was measured at 48 h (in 5 patients) and 7 days (in 6 patients). Except for an occasional 1-hour peritoneal fluid sample on the 7th day, all samples had satisfactory vancomycin levels. Five of the 8 patients who had gram-positive peritonitis and 1 with 'sterile' peritonitis received another similar intraperitoneal dose of vancomycin at the 7th day. All of these patients had good therapeutic response with a negative PD culture 3 weeks after the cessation of therapy and no relapse of infection in at least 1 month of follow-up. We conclude that 2 intraperitoneal doses of vancomycin (30 mg/kg body weight) given 1 week apart with 6 h of intraperitoneal dwell is an effective and adequate treatment for gram-positive and 'sterile' peritonitis in CAPD patients.     

Use of intraperitoneal urokinase for resistant bacterial peritonitis in continuous ambulatory peritoneal dialysis

Intraperitoneal (IP) urokinase is a fibrinolytic agent that has been used in the adjunctive treatment of continuous ambulatory peritoneal dialysis (CAPD) and resistant and relapsing peritonitis. However, its efficacy and role in treating resistant CAPD bacterial peritonitis remain unclear and results from previous prospective studies have been conflicting. We prospectively randomized 88 CAPD patients with bacterial peritonitis resistant to initial empirical IP antibiotics into two groups: IP urokinase 60,000 IU and a placebo group. Patients were treated concomitantly with susceptible antibiotics according to culture results. Peritoneal dialysate grew pseudomonas aeruginosa in 13 patients (14.8%), non-pseudomonas bacteria in 63 patients (71.6%) and negative cultures in 12 patients (13.6%). For the clinical outcomes, there were no significant differences in the primary response rates (61.4 vs. 50%), relapse rates (9.1 vs. 13.6%), Tenckhoff catheter removal rates (22.7 vs. 29.5%) and mortality rates (6.8 and 6.8%) between the urokinase group and the controls (p=ns). Subgroup analysis of culture negative patients (n=12) also demonstrated no sgnificant benefit for urokinase treatment. No significant adverse effects were encountered with the IP urokinase instillation. Total median peritonitis-related length of hospitalization for the urokinase group and controls were 7 and 11 days, respectively (p=0.32). We concluded that IP urokinse plays no significant role as an adjuvant therapy in the treatment of bacterial CAPD peritonitis resistant to initial IP antibiotic therapy.     

Leptin in peritoneal dialysate from continuous ambulatory peritoneal dialysis patients.

The adipocyte-derived hormone leptin is the 16-kd product of the ob gene that regulates food intake and body weight. Plasma leptin level is elevated in patients with chronic renal failure, partly because of impaired clearance through the kidney. In this study, we examined whether leptin is cleared into peritoneal dialysate in patients with end-stage renal disease treated by continuous ambulatory peritoneal dialysis (CAPD). The subjects were 46 CAPD patients and 67 age- and gender-matched healthy subjects. Leptin concentration in peritoneal dialysate from CAPD patients was measurable by a sensitive enzyme-linked immunosorbent assay (ELISA), and the daily loss of leptin by the peritoneal route was estimated to correspond to the amount contained in approximately 2 L plasma. Dialysate leptin concentration correlated positively with plasma leptin level and with percent body fat measured by dual-energy X-ray absorptiometry. The dialysate-to-plasma (D/P) ratio of leptin concentration was twice higher than expected from its molecular weight. D/P ratios of beta2-microglobulin, albumin, and transferrin showed strong correlations with each other (r = 0.768 to 0.801), whereas the correlation between D/P ratios of leptin and beta2-microglobulin was less impressive (r = 0.378). This was also the case with the relationship between apparent peritoneal clearances of these macromolecules, suggesting that dialysate leptin had some origins other than passive transport of plasma leptin. To test the hypothesis that abdominal visceral fat may contribute to the unexpectedly raised peritoneal dialysate leptin concentration, multiple regression analysis was performed. Leptin concentration in peritoneal dialysate showed significant association with plasma leptin level and D/P ratio of beta2-microglobulin, and it also showed an independent association with abdominal visceral fat but not with subcutaneous fat assessed by ultrasonography. These results showed that peritoneal dialysate from CAPD patients contained a significant amount of leptin, which derived presumably from both plasma and local visceral fat tissue.     

Congestive cardiomyopathy in patients on continuous ambulatory peritoneal dialysis

We present a report of cardiac dilatation and symptomatic congestive heart failure in two patients receiving treatment with continuous ambulatory peritoneal dialysis (CAPD). Both patients had previous partial parathyroidectomies and persistent hypocalcemia prior to the development of a congestive cardiomyopathy. The hypocalcemia was unresponsive to treatment with activated vitamin D therapy; however, intravenous replenishment of the ionized serum calcium level was accompanied by improvement in cardiac functional parameters. In one of the two patients, chronic calcium repletion with high dialysate calcium was associated with significant improvement in cardiac symptoms and a decrease in left ventricular dilatation. These observations suggest that partial parathyroidectomy and associated hypocalcemia place patients on CAPD at increased risk of cardiac dysfunction.     

Tuberculous lymphadenitis in patients undergoing continuous ambulatory peritoneal dialysis

The aim of this study was to review the clinical features of tuberculous (TB) lymphadenitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Nine cases of TB lymphadenitis were diagnosed among 910 patients over a period of 10 years. There were five men and four women with a mean age of 51 ± 15.5 years. The TB lymphadenitis involved the cervical lymph nodes in six patients, supraclavicular lymph nodes in two patients and mediastinal lymph nodes in one patient. Six patients presented with clinically enlarged lymph nodes of whom four also had fever. Three other patients were incidentally found to have enlarged lymph nodes on routine chest X-ray or ultrasound examination of the neck. Diagnosis of TB lymphadenitis was made by demonstrating caseating granulomata with or without positive acid-fast bacilli on excisional lymph node biopsy. All patients were cured with standard anti-tuberculosis drugs for 12 months. No recurrence of the TB lymphadenitis was observed after a mean follow-up of 59 ± 30 months. We conclude that TB lymphadenitis is not uncommon among patients on CAPD. A high index of suspicion is needed for early diagnosis of this condition. Prompt initiation of anti-tuberculosis treatment is associated with good prognosis.     

Ofloxacin pharmacokinetics in patients on continuous ambulatory peritoneal dialysis

Pharmacokinetics of ofloxacin (OFX) was studied in patients on continuous ambulatory peritoneal dialysis (CAPD) carrying out three exchanges per day. In 11 patients given 300 mg of OFX orally, serum OFX concentration peaked at 2.44 mg/l 3.7 hours after administration and the mean elimination half-life of OFX was 25 hours. OFX concentrations in peritoneal fluid underwent cyclical changes with each change of solutions, reaching beyond 0.5 mg/l after 2 hours of equilibration. There was a highly significant correlation between corresponding serum and peritoneal fluid concentrations of OFX after an 8 h equilibration (r = 0.85, p less than 0.001). In 5 patients given a 400 mg loading dose followed by 200 mg of OFX per day for 7 days, trough serum OFX concentrations ranged from 1.35 to 7.00 mg/l and no adverse effects were noticed. CAPD per exchange removed less than 2% of the total dose of OFX given.     

Albumin homeostasis in patients undergoing continuous ambulatory peritoneal dialysis

Albumin and protein removal rates were studied in 18 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). In nine patients simultaneous studies of albumin distribution and turnover were performed. Total albumin loss was 4.23 +/- 1.42 g/1.73 m2/24 hr; total protein removed was 8.79 +/- 4.21 g/1.73 m2/24 hr. Although these values were well within the range for severe nephrosis, serum albumin concentration remained nearly normal, 3.7 +/- 0.5 g/dl. Plasma albumin mass, 120.0 +/- 25.2 g/1.73 m2, and total albumin mass, 249 +/- 29.1 g/1.73 m2, did not differ from those of the control group. Compared with the control group, patients had reduced albumin catabolism, 9.76 +/- 1.74 g/1.73 m2/24 hr versus 13.8 +/- 0.77 g/1.73 m2/24 hr (P less than 0.001). Within the patient group albumin synthesis increased with increased albumin loss. Serum albumin concentration correlated negatively with albumin losses (P less than 0.001). The CAPD patients maintained albumin homeostasis through decreased albumin catabolism and increased synthesis. All major albumin pools were maintained despite massive albumin loss.