Hyperkalemia due to compound sulfamethoxazole in a patient after kidney transplantation
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A 56-year-old female patient received triple-drug immunosuppressive therapy after allogenic renal transplantation, including tacrolimus 3 mg twice daily, mycophenolate mofetil 500 mg twice daily, and prednisone 20 mg once daily. The patient received compound sulfamethoxazole 0.48 g once daily for prevention of infection a month after operation. The laboratory tests showed that the levels of tacrolimus blood concentration (CTac), serum creatinine (Scr), and blood potassium were 6.56 μg/L, 142 μmol/L, and 4.3 mmol/L, respectively before medication, 12.13 μg/L, 147 μmol/L, and 7.1 mmol/L after 1 week of compound sulfamethoxazole treatment, and 16.72 μg/L, 176 μmol/L, and 8.3 mmol/L after 2 weeks, accompanied by lassitude and weakness of the feet. Compound sulfamethoxazole was stopped, potassium-lowering therapy was given, the dose of tacrolimus was reduced to 2 mg twice daily, and mycophenolate mofetil and prednisone were given at the same doses as before. Laboratory tests showed Scr 175 μmol/L and blood potassium 4.7 mmol/L on day 3 of compound sulfamethoxazole withdrawal and CTac 7.13 μg/L, Scr 150 μmol/L, and blood potassium 4.8 mmol/L on day 8. The patient took compound sulfamethoxazole 0.48 g twice daily again according to the doctor′s advice, and 2 weeks later, her blood potassium increased to 6.2 mmol/L. The dose of compound sulfamethoxazole was gradually reduced firstly to 0.48 g once daily, then to 0.48 g every other day, and was completely stopped 8 weeks later. Two weeks after drug withdrawal, her blood potassium decreased to 4.6 mmol/L. Hyperkalemia did not recur.
Key words:
Kidney transplantation; Sulfonamides; HyperkalemiaKeywords:
Sulfamethoxazole
In severe, sometimes life-threatening infections azlocillin (Securopen) is administered in single doses up to 10 g in order to increase therapeutic efficacy. Therefore the serum concentrations and urinary excretion of azlocillin were investigated in 2 healthy volunteers and in 11 patients after intravenous injection (5 min) of 2 g followed by intravenous infusion of 2 g/h over 4 h. The serum concentrations increased during infusion in patients up to a median concentration of 317 mg/l. The median serum concentrations decreased down to 94 mg/l at 2 h, 43 mg/l at 4 h and 11 mg/l at 6 h after the end of infusion. 24-h urinary excretion in patients was 54.3%. Serum half-life from the last five serum concentrations (6-10 hours after start of administration) calculated amounts to a median half life of 100 min (range 60-180 min). The study showed, that using this dose and kind of administration high serum concentrations can be maintained over many hours, sufficiently high also for life threatening and difficult-to-treat infections, if administered at intervals of 12 hours.
Azlocillin
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Intravenous Infusions
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Vinblastine sulfate was administered to 28 patients as a continuous infusion for five consecutive days in doses of 0.75 to 2.0 mg/m2. Pharmacokinetic studies in 4 patients showed that plasma levels increased rapidly after beginning the infusion with a steady state occurring in 10-48 hours at 2 ng/ml for 1.25 mg/m2, and 5-8 ng/ml for 2.0 mg/m2. The T 1/2 b after completion of the infusion was 19 hours. Dose-limiting toxicity was myelosuppression. A partial remission of four months duration was observed in a patient with adenocarcinoma of the gastroesophageal junction. One patient, who had been heavily pretreated, obtained partial remission while three patients with breast cancer had a minor response. There was no response in 10 patients with hypernephroma. The suggested starting dose is 2 mg/m2 for un-pretreated cases and 1.75 mg/m2 daily for 5 consecutive days monthly for prior treated cases.
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A 46-year-old woman received an IV infusion of piperacillin sodium/tazobactam sodium 4.5g every 8 hours for postoperative intracranial infection.Her WBC count decreased from 10.61×109/L before treatment to 1.79×109/L on day 13 of treatment and 1.00×109/L on day 15 of treatment,respectively.Piperacillin/tazobactam was withdrawn immediately and switched to other antibacterial drugs,and then hypodermic recombinant human granulocyte macrophage colony stimulating factor(rhGM-CSF)150 μg once daily was given.Four days after the treatment changes,her WBC count increased to 6.95×109/L.Six days after the treatment changes,her cerebrospinal fluid WBC count increased from 8×106/L(15 days after the first administration) to 56×106/L,she was readministered an IV infusion of piperacillin /tazobactam 4.5 g every 8 hours and her rhGM-CSF dosage remained unchanged.After a 6-day treatment,her intracranial infection was cured,antibacterial drugs were stopped.On days 2 and 5 of treatment,her WBC count was 2.67×109/L and 1.65×109/L,respectively.On day 8,rhGM-CS was withdrawn and WBC count was 5.75×109/L.On day 15,WBC count was 4.56×109/L.
Piperacillin/tazobactam
Leukopenia
Tazobactam
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Pharmacological studies of ceftriaxone, a new semisynthetic cephalosporin, were conducted in 35 cancer patients. This antibiotic was administered in a variety of doses and schedules with no observed toxicity. Intramuscular administration of 500 mg of ceftriaxone to seven patients produced mean peak serum concentrations of 32.9 μg/ml 2.0 h after administration. The terminal serum half-life was 10.9 h. Intravenous infusion of 500 mg of ceftriaxone over 5 min to the same group of seven patients produced a mean peak concentration of the drug in serum of 83 μg/ml at the end of administration which decreased to 16.8 μg/ml at 8 h. A dose of 1 g of ceftriaxone given in identical fashion to the same group of seven patients produced mean peak concentrations in serum of 130 μg/ml at the end of administration and 17.3 μg/ml at 12 h. The mean percentages of drug recovered in urine 12 h after single intravenous doses of 500 mg and 1 g were 30 and 20%, respectively. A 1-g dose of ceftriaxone was administered every 8 h to 10 patients, and a 2-g dose was administered every 12 hours to 9 patients. Drug concentrations in serum were measured for each patient after drug administration on day 1, day 3 or 4, and day 7 or 8. The 1-g dose produced an observed mean peak concentration of 154 μg/ml and a mean terminal-phase half-life of 5.6 h on day 3 or 4. The 2-g dose produced a mean peak concentration in serum of 262 μg/ml and a terminal-phase serum half-life of 6.3 h on day 3 or 4. Continuous infusion studies were performed in nine neutropenic patients for up to 8 days by using a loading dose of 1 g over 30 min, followed by 2 g every 8 h. Mean concentrations in serum were maintained at about 135 μg/ml during the infusion period.
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Objective To investigate the relationship between dose and trough blood concentration of tacrolimus after orthotopic liver transplantation and the changes of time-dependent concentration. Methods The doses and trough blood concentrations of tacrolimus from 20 patients who survived longer than 1 year were summarized retrospectively.Results The initial oral doses of 0.15 mg·kg -1·d -1 as suggested by most surgeons led to 53.4 % of the measured whole blood concentrations in the first postoperative week were higher than 15 μg/L, 23.3 % of them within 10 μg/L to 15 μg/L and 23.3 % of them lower than 10 μg/L. The ratio of trough concentration/dose was increased gradually after transplantation and reached its peak at the second postoperative month, which was higher than those in the following month 3, 4, 5, 6, 7, 8 and 11 significantly (all P 0.05). The average ratio of concentration/dose for 20 patients in one year of time was 190.3± 75.4. The dosage to maintain the required ideal treatment trough blood concentration from 10 μg/L to 15 μg/L in the first postoperative week was 0.101 37± 0.026 10 mg·kg -1·d -1. Following the decrease of the required treatment concentration, the ideal dosage was reduced to 0.064 66± 0.027 97 mg·kg -1·d -1 at the end of one year.Conclusion The tacrolimus should be given at a dose of about 0.1 mg·kg -1·d -1 initially after OLT under the current situation in China. The oral bioavailability of tacrolimus in liver transplantation recipients in China were higher than that reported by surgeons from other country. The ratio of concentration/dose in the second postoperative month was higher than the following month 3, 4, 5, 6, 7, 8 and 11.
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A 25-year-old male patient with upper abdominal pain for 3 hours received combination treatment with famotidine tablets 20 mg twice daily and 2 roter tablets thrice daily.After 2 days of treatment, his upper abdominal pain became worse than before,liver function tests showed the following levels:alanine aminotransferase(ALT) 178 U/L.Then he received an IV infusion of famotidine 20 mg and glucurolactone 266 mg twice daily.On day 2 of hospitalization,liver function tests showed the following levels:ALT 133 U/L,aspartate aminotransferase(AST) 63 U/L,γ-glutamyl transferase(γ-GT)162 U/L;on day 8 of hospitalization,repeat liver function tests revealed the following levels:ALT 414 U/L,AST 134 U/L,γ-GT 714 U/L,alkaline phosphatase 161 U/L,total bilirubin(TBil) 15.2 μmol/L,direct bilirubin(DBil) 9.7 μmol/L,so it was considered that the liver damage may be associated with famotidine,then famotidine was discontinued immediately and switched to an Ⅳ infusion of pantoprazole sodium 40 mg in 0.9%sodium chloride 100 ml twice daily.An Ⅳ infusion of reduced glutathione 1.8 g and compound glycyrrhizin 160 mg in 5%glucose 250 ml once daily was given.Five days after famotidine withdrawal,repeat liver function tests revealed the following levels:ALT 62 U/L,γ-GT 315 U/L,TBil 13.1 μmol/L,DBil 6.2 μmol/L.A week later,his liver function tests revealed the following levels:ALT 28 U/L,AST 31 U/L.
Famotidine
Liver function
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A 73-year-old woman with chronic bronchitis, pulmonary interstitial fibrosis, bronchiectasis concurrent infection received an IV infusion of levofloxacin 0.4 g once daily. One week later, her symptoms were not improved. An IV infusion of tigecycline 50 mg twice daily was added to her regimen according to sputum culture results and drug sensitivity test. Nine days later, the patient developed nausea and vomiting. Laboratory tests showed serum urea value of 36.5 mmol/L and amylase 1 166 U/L. Tigecycline was replaced by IV infusion of imipenem and cilastatin sodium 1.0 g thrice daily, and levofloxacin continued. Octreotide acetate and pantoprazole sodium were given. Fasting and fluid supplement were applied. One week later, the nausea and vomiting disappeared. Her serum urea and amylase were 8.1 mmol/L and 42 U/L, respectively.
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Tigecycline; Urea; Amylases
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Acute intoxications with salicylates are common. In a dosage of 150-300 mg/kg they are severe, and above 500 mg/kg potentially fatal. To commit suicide 4 patients ingested 375-460 mg/kg acetylsalicylic acid; 3-8 hours after ingestion salicylate blood levels of up to 760 mg/l were observed. The patients were treated for a period of 16 hours with oral charcoal and glycine (1 g/kg initially, followed every 4 hours by 0.5 g/kg, and 8 g initially, followed by 4 g, respectively). To increase urinary pH (7-9) they received i.v. NaHCO3. Blood levels of salicylic acid including its metabolites dropped initially with a virtual half-life of 2-4 hours. 18 hours after hospital admission every patient was in good general condition; none of them required hemodialysis. The urinary excretion of total salicylate reached only 6-14% of the dose within the first 12 hours of therapy, clearly indicating the importance of combined therapy with glycine and charcoal in achieving a good clinical outcome.
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A Phase I study of protracted continuous infusion 5-fluorouracil was undertaken at a starting dose of 200 mg/m2/day. The drug was delivered via a tunneled subclavian venous access site by a portable infusion pump (Cor-Med) permitting ambulatory monitoring. Seventeen patients were administered 19 courses at incremental dose rates from 200 mg/m2/day to 600 mg/m2/day; treatment was terminated at the onset of stomatitis. At dose rates of 300 mg/m2/day or less, the treatment did not require interruption for up to 60 days or up to 36 g cumulative dose. For dose rates of 350 to 600 mg/m2/day, the treatment always required interruption: mean duration 20 day for 350 mg/m2/day; 9 day for 400 mg/m2/day; and 14 day for 600 mg/m2/day. Mean cumulative dose at the higher dose rates was 10.9 g (350 mg/m2/day); 7.9 g (400 mg/m2/day); and 15.3 g (600 mg/m2/day). Mean cumulative dose at 200 mg/m2/day was 11.5 g and at 300 mg/m2/day, was 22.6 g. Protracted venous infusion allows for a substantial cumulative dose of 5-FU and at dose rate delivery of 300 mg/m2/day may be administered for up to 60 days without adverse effects due to the drug or to the presence of an indwelling venous access line.
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Netilmicin
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