Pharmacokinetics of Dirithromycin in Patients with Mild or Moderate Cirrhosis

1999 ◽  
Vol 43 (7) ◽  
pp. 1556-1559 ◽  
Author(s):  
Teresita Mazzei ◽  
Calogero Surrenti ◽  
Andrea Novelli ◽  
Maria Rosa Biagini ◽  
Stefania Fallani ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Volume Of Distribution ◽  
Time Curve ◽  
Class A ◽  
Elimination Half ◽  
Class B ◽  
Child's Classification ◽  
Cirrhotic Patients ◽  
The Mean ◽  
Limited Basis

ABSTRACT The pharmacokinetics of dirithromycin were determined over a 72-h period following oral administration of a single 500-mg dose to 8 healthy volunteers and to 16 cirrhotic patients (8 patients with class A cirrhosis and 8 patients with class B cirrhosis according to Pugh’s & Child’s classification). Drug levels in plasma and urine were determined by microbiological assay. The mean maximum concentrations of drug in serum obtained 3 to 4 h after administration were 0.29 ± 0.22 mg/liter in volunteers and 0.48 ± 0.21 and 0.52 ± 0.38 mg/liter in patients with class A and class B cirrhosis, respectively. The elimination half-life (t 1/2β) was 23.3 ± 7.6 h in healthy subjects and 35.2 ± 11.8 h and 39.5 ± 11.0 h in patients with class A and class B cirrhosis, respectively. The mean area under the concentration-time curve (AUC) and t 1/2β were significantly higher in patients with class A and B cirrhosis than in healthy controls, while total and renal clearances were markedly reduced (P < 0.01). The time to the maximum concentration of drug in serum and the volume of distribution values appeared to be similar in all groups, and the mean recovery in urine at 72 h ranged from 3.7 to 5.7%, without significant differences among groups. These results demonstrate that some dirithromycin kinetic parameters are significantly different in cirrhotic patients in comparison to those in healthy volunteers. However, an increase in the t 1/2β or AUC, which is also observed with other semisynthetic macrolides (e.g., azithromycin), does seem to be not clinically relevant if one takes into account both the high therapeutic indices of these antibiotics and the usually short duration of therapy. Therefore, on the limited basis of single-dose administration, no modifications of dirithromycin dosage seem to be required even for patients with class B liver cirrhosis.

Cardiomyopathy in Cirrhotic Patients and Its Relationship with the Severity of Cirrhosis

2021 ◽  
Vol 15 (10) ◽  
pp. 2779-2782
Author(s):  
Saira Khalid ◽  
Nasir Shah ◽  
Yasir Abbas Zaidi ◽  
Muhammad Saleem Hasan ◽  
Saqib Jahangir ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Severe Disease ◽  
P Value ◽  
Cirrhotic Cardiomyopathy ◽  
Male Predominance ◽  
Class A ◽  
Class B ◽  
Cirrhotic Patients ◽  
The Mean ◽  
Class C

Study Objectives: To determine the frequency of cirrhotic cardiomyopathy in patients with liver cirrhosis and to compare it across varying grades of cirrhosis on Child Turcotte Pugh classification. Study Design and Settings: It was a descriptive cross-sectional study carried at Department of Medicine, Lahore General Hospital Lahore over 1 year from Jan 2018 to Dec 2018. Patients and Methods: The present research involved 100 male and female patients aged between 16-70 years having liver cirrhosis diagnosed at least 6 months ago. These patients underwent echocardiographic screening of cardiomyopathy which was diagnosed by the presence of diastolic dysfunction (i.e. increased E/A ratio>1). An informed written consent was obtained from every patient. Results of the Study: There was a male predominance (M:F, 1.6:1) among cirrhotic patients with a mean age of 51.9±9.8 years. The mean BMI was 26.5±3.7 Kg/m2 while the mean duration of cirrhosis was 22.0±10.9 months. Majority (49.0%) of the patients belonged to CTP Class C followed by Class-B (39.0%) and Class-A (12.0%). Cirrhotic cardiomyopathy was observed in 41.0% patients with cirrhosis. There was statistically insignificant difference in the observed frequency of cirrhotic cardiomyopathy among various subgroups of cirrhotic patients depending upon patient’s age (p-value=0.928), gender (p-value=0.997), BMI (p-value=0.983) and duration of disease (p-value=0.782). However, it increased considerably with worsening of disease on CTP Classification; Class-A vs. Class-B vs. Class-C (8.3% vs. 35.9% vs. 53.1%; p-value=0.013). Conclusion: Cirrhotic cardiomyopathy was observed in a substantial proportion of cirrhotic patients and was more frequent in patients with more severe disease which warrants routine echocardiographic screening of cirrhotic patients so that timely recognition and anticipated treatment of this complication may improve the case outcome in future medical practice. Keywords: Cirrhosis, Cardiomyopathy, Child Turcotte Pugh Class

scholarly journals Safety, toleration, and pharmacokinetics of intravenous azithromycin.

1996 ◽  
Vol 40 (11) ◽  
pp. 2577-2581 ◽  
Author(s):  
D R Luke ◽  
G Foulds ◽  
S F Cohen ◽  
B Levy
Keyword(s):  
Half Life ◽  
Active Drug ◽  
Slow Release ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Concentration Time ◽  
Elimination Half ◽  
The Mean ◽  
Male Subjects

To date, the clinical pharmacology of large intravenous doses of azithromycin has not been described. In the present study, single 2-h intravenous infusions of 1, 2, and 4 g of azithromycin were administered to three parallel groups (in each group, six received active drug and two received placebo) of healthy male subjects. Toleration (assessed by scores of subject-administered visual analog scale tests spanning 0 [good] to 10 [poor]), safety, pharmacokinetics, and serum motilin levels were monitored for up to 240 h after the start of each intravenous infusion. Mean nausea scores of 0.0, 0.0, 1.0, and 0.5 and abdominal cramping scores of 0.0, 0.0, 0.4, and 0.4 for 12-h periods after doses of 0, 1, 2, and 4 g of azithromycin, respectively, suggested that azithromycin was well tolerated. Because of the standardized 1-mg/ml infusates, all subjects in the 4-g dosing group complained of an urgent need to urinate. There were no consistent trends in endogenous motilin levels throughout the study. The maximum concentration of azithromycin in serum (10 micrograms/ml after a 4-g dose) and the area under the concentration-time curve (82 micrograms.h/ml after a 4-g dose) were dose related. The mean pharmacokinetic parameters were an elimination half-life of 69 h, total systemic clearance of 10 ml/min/kg, and a volume of distribution at steady state of 33.3 liters/kg. The pharmacokinetic results suggest that the long half-life of azithromycin is due to extensive uptake and slow release of the drug from tissues rather than an inability to clear the drug. Single intravenous doses of up to 4 g of azithromycin in healthy subjects are generally well tolerated, and quantifiable concentrations may persist in serum for 10 days or more.

scholarly journals Population pharmacokinetic study of isepamicin with intensive care unit patients.

1996 ◽  
Vol 40 (4) ◽  
pp. 983-987 ◽  
Author(s):  
M Tod ◽  
C Padoin ◽  
C Minozzi ◽  
J Cougnard ◽  
O Petitjean
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Healthy Volunteers ◽  
Half Life ◽  
Volume Of Distribution ◽  
Multivariate Linear Regression Analysis ◽  
Icu Patients ◽  
Elimination Half Life ◽  
Elimination Half ◽  
The Mean

The pharmacokinetics (PK) of isepamicin, a new aminoglycoside, were studied in 85 intensive care unit (ICU) patients and were compared with those observed in 10 healthy volunteers. A parametric method based on a nonlinear mixed-effect model was used to assess population PK. Isepamicin was given intravenously over 0.5 h at dosages of 15 mg/kg once daily or 7.5 mg/kg twice daily. The data were fitted to a bicompartmental open model. Compared with healthy volunteers, the mean values of the PK parameters were profoundly modified in ICU patients: elimination clearance was reduced by 48%, the volume of distribution in the central compartment (Vc) was increased by 50%, the peripheral volume of distribution was 70% higher, the distribution clearance was 146% lower, and the elimination half-life was ca. 3.4 times higher. The interindividual variability in PK parameters was about 50% in ICU patients. Five covariates (body weight [BW], simplified acute physiology score [SAPS], temperature, serum creatinine level, and creatinine clearance [CLCR]) were tentatively correlated with PK parameters by multivariate linear regression analysis with stepwise addition and deletion. The variability of isepamicin clearance was explained by three covariates (BW, SAPS, and CLCR), that of Vc was explained by BW and SAPS, and that of the elimination half-life was explained by CLCR and SAPS. Simulation of the concentration-versus-time profile for 500 individuals showed that the mean peak (0.75 h) concentration was 18% lower in ICU patients than in healthy volunteers and that the range in ICU patients was very broad (28.4 to 95.4 mg/liter). Therefore, monitoring of the isepamicin concentration is in ICU patients is mandatory.

scholarly journals Antimalarial Bioavailability and Disposition of Artesunate in Acute Falciparum Malaria

2000 ◽  
Vol 44 (4) ◽  
pp. 972-977 ◽  
Author(s):  
Paul Newton ◽  
Yupin Suputtamongkol ◽  
Paktiya Teja-Isavadharm ◽  
Sasithon Pukrittayakamee ◽  
V Navaratnam ◽  
...  
Keyword(s):  
Falciparum Malaria ◽  
Antimalarial Activity ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Time Curve ◽  
Elimination Half ◽  
Pharmacokinetic Properties ◽  
Absolute Oral Bioavailability ◽  
The Mean ◽  
Apparent Volume Of Distribution

ABSTRACT The pharmacokinetic properties of oral and intravenous artesunate (2 mg/kg of body weight) were studied in 19 adult patients with acute uncomplicated Plasmodium falciparum malaria by using a randomized crossover design. A sensitive bioassay was used to measure the antimalarial activity in plasma which results from artesunate and its principal metabolite, dihydroartemisinin. The oral study was repeated with 15 patients during convalescence. The mean absolute oral bioavailability of the antimalarial agent in patients with acute malaria was 61% (95% confidence interval [CI], 52 to 70%). The absorption and elimination of oral artesunate were rapid, with a mean elimination half-life of antimalarial activity of 43 min (95% CI, 33 to 53 min). Following oral administration to patients with acute falciparum malaria, peak antimalarial activity in plasma and the area under the plasma concentration-time curve were approximately double those during convalescence and the apparent volume of distribution and clearance were approximately half those during convalescence (P ≤ 0.005). Acute malaria is associated with a significant reduction in the clearance of artesunate-associated antimalarial activity.

scholarly journals Comparison of Doppler waveform and mean velocity of hepatic vein in cirrhotic patients with healthy subjects and their correlation with severity of cirrhosis

2014 ◽  
Vol 3 (2) ◽  
pp. 23-28
Author(s):  
Mahzabeen Islam ◽  
Akhter Uddin Ahmed ◽  
AS Mohiuddin
Keyword(s):  
Hepatic Vein ◽  
Healthy Subjects ◽  
Wave Form ◽  
Case Group ◽  
Mean Velocity ◽  
Class A ◽  
Doppler Waveform ◽  
Class B ◽  
Cirrhotic Patients ◽  
The Mean

This descriptive study was carried out in the Department of Radiology and Imaging, BIRDEM (Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorder) Dhaka during the period of 1st June 2008 to 30th May 2009, to compare the pattern of the Doppler waveform and mean velocity of hepatic vein between healthy subjects and that in cirrhotic patients and to detect possible differences and also to assess the accuracy of the detection of changes in hepatic vein waveform and mean velocity for the diagnosis of liver cirrhosis. A total of 40 cirrhotic patients and 40 healthy subjects were enrolled in this study. Doppler waveform was done in all the patients and the healthy subjects. The mean hepatic vein velocity (MHVV) was 12.22±4.22 cm/sec and 5.17±1.19 cm/sec in case and healthy group respectively. The mean MHVV difference was significantly (p<0.001) higher in case group. 37.5% patient had wave form HV-0 and HV-1 and 25.0% had wave form HV-2 in case group, however, in healthy group all subjects had wave form HV-0 and the difference was statistically significant (p<0.05) between case and healthy. In Child's class A wave form HV-0 was found in 75.0%, HV-1 was 25.0% and HV-2 was not found in case group. In Child's class B wave form HV-0 was found in 21.4%, HV-1 was 71.5% and HV-2 was 7.1%. In Child's class C wave form HV-0 was not found, HV-1 was 10.0% and HV-2 was 90.0%. The and the difference was statistically significant (p<0.05) among the different grading level with wave form. In Child's class A the mean velocity was 9.18±1.81 cm/sec and velocity ranged from 7.5 to 14.2 cm/sec. In Child's class B the mean velocity was 11.26 ±1.81 cm/sec and velocity ranged from 7.5 to 14.2 cm/sec. In Child's class C the mean velocity was 18.44±1.91 cm/sec and velocity ranged from 15.5 to 20.9 cm/sec. The mean velocity was statistically significant (p<0.05) among Child's class A, Child's class B and Child's class C. From the above summary and previous study it is observed that there is a significant difference between Doppler waveform and mean velocity of right hepatic vein in cirrhotic patients and in normal subjects. It can be used as a new parameter in the assessment of liver cirrhosis. CBMJ 2014 July: Vol. 03 No. 02 P: 23-28

scholarly journals Some kinematics of halo coronal mass ejections

2020 ◽  
Vol 29 (1) ◽  
pp. 81-88
Author(s):  
Virendra Kumar Verma ◽  
Nishant Mittal ◽  
Ramesh Chandra
Keyword(s):  
Coronal Mass Ejections ◽  
Solar Flares ◽  
Coronal Holes ◽  
Geomagnetic Disturbances ◽  
Class A ◽  
Heliospheric Physics ◽  
Class B ◽  
The Mean ◽  
Class C

AbstractWe present an investigation of halo coronal mass ejections (HCMEs) kinematics and other facts about the HCMEs. The study of HCMEs is very important because HCMEs are regarded as the main causes of heliospheric and geomagnetic disturbances. In this study, we have investigated 313 HCMEs observed during 1996-2012 by LASCO, coronal holes, and solar flares. We find that HCMEs are of two types: accelerated HCMEs and decelerated HCMEs. The mean space speed of HCMEs is 1283 km/s while the mean speed of decelerated HCMEs and accelerated HCMEs is 1349 km/s and 1174 km/s, respectively. The investigation shows that 1 (0.3%) HCME was associated with class A SXR, 14 (4.7%) HCMEs were associated with class B SXR-flares, 87 (29.4%) HCMEs were associated with class C SXR-flares, 125 (42.2%) HCMEs were associated with class M SXR-flares and 69 (23.3%) HCMEs were associated with class X SXR-flares. The speed of HCMEs increases with the importance of solar SXR-flares. The various results obtained in the present analysis are discussed in the light of the existing scenario of heliospheric physics.

scholarly journals Normalisation of the psychometric encephalopathy score within the Cameroonian population

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Larissa Pessidjo Djomatcho ◽  
Mathurin Pierre Kowo ◽  
Antonin Ndjitoyap Ndam ◽  
Sylvain Raoul Simeni Njonnou ◽  
Gabin Ulrich Kenfack ◽  
...  
Keyword(s):  
Hepatic Encephalopathy ◽  
Healthy Volunteers ◽  
Clinical Signs ◽  
Minimal Hepatic Encephalopathy ◽  
Education Level ◽  
Multicentric Study ◽  
Tracing Test ◽  
Cirrhotic Patients ◽  
The Mean ◽  
Number Connection Test

Abstract Background Minimal hepatic encephalopathy (MHE) is the presence of neuropsychological abnormalities detectable by psychometric tests. Psychometric Hepatic Encephalopathy Score (PHES) is a gold standard test for the early diagnosis of MHE in cirrhotic patients. The aim of this study was to standardize the PHES in a healthy Cameroonian population and to evaluate the prevalence of MHE among cirrhotic patients. Methods This was a prospective, multicentric study from 1 December 2018 to 31 July 2019 in two groups: healthy volunteers and cirrhotic patients without clinical signs of hepatic encephalopathy. The results of the number connection test-A, number connection test-B, serial dotting test, line tracing test were expressed in seconds and those of the digit symbol test in points. Results A total of 102 healthy volunteers (54 men, 48 women) and 50 cirrhotic patients (29 men, 31 women) were included. The mean age was 38.1 ± 12.55 years in healthy volunteers and 49.3 ± 15.6 years in cirrhotic patients. The mean years of education level was 11.63 ± 4.20 years in healthy volunteers and 9.62 ± 3.9 years in cirrhotic patients. The PHES of the healthy volunteer group was − 0.08 ± 1.28 and the cut-off between normal and pathological values was set at − 3 points. PHES of the cirrhotic patients was − 7.66 ± 5.62 points and significantly lower than that of volunteers (p < 0.001). Prevalence of MHE was 74% among cirrhotic patients. Age and education level were associated with MHE. Conclusion PHES cut-off value in Cameroonians is − 3, with MHE prevalence of 74% among cirrhotic patients.

scholarly journals Serum bactericidal activities and comparative pharmacokinetics of meropenem and imipenem-cilastatin.

1996 ◽  
Vol 40 (1) ◽  
pp. 105-109 ◽  
Author(s):  
M Dreetz ◽  
J Hamacher ◽  
J Eller ◽  
K Borner ◽  
P Koeppe ◽  
...  
Keyword(s):  
Compartment Model ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Dose Administration ◽  
Microdilution Method ◽  
Two Compartment Model ◽  
Elimination Half ◽  
Renal Clearances ◽  
The Mean ◽  
Bactericidal Activities

The pharmacokinetics and serum bactericidal activities (SBAs) of imipenem and meropenem were investigated in a randomized crossover study. Twelve healthy male volunteers received a constant 30-min infusion of either 1 g of imipenem plus 1 g of cilastatin or 1 g of meropenem. The concentrations of the drugs in serum and urine were determined by bioassay and high-pressure liquid chromatography. Pharmacokinetic parameters were based on an open two-compartment model and a noncompartmental technique. At the end of infusion, the mean concentrations of imipenem and meropenem measured in serum were 61.2 +/- 9.8 and 51.6 +/- 6.5 mg/liter, respectively; urinary recoveries were 48.6% +/- 8.2% and 60.0% +/- 6.5% of the dose in 12 h, respectively; and the areas under the concentration-time curve from time zero to infinity were 96.1 +/- 14.4 and 70.5 +/- 10.3 mg.h/liter, respectively (P < or = 0.02). Imipenem had a mean half-life of 66.7 +/- 10.4 min; that of meropenem was 64.4 +/- 6.9 min. The volumes of distribution at steady state of imipenem and meropenem were 15.3 +/- 3.3 and 18.6 +/- 3.0 liters/70 kg, respectively, and the mean renal clearances per 1.73 m2 were 85.6 +/- 17.6 and 144.6 +/- 26.0 ml/min, respectively. Both antibiotics were well tolerated in this single-dose administration study. The SBAs were measured by the microdilution method of Reller and Stratton (L. B. Reller and C. W. Stratton, J. Infect. Dis. 136:196-204, 1977) against 40 clinically isolated strains. Mean reciprocal bactericidal titers were measured 1 and 6 h after administration. After 1 and 6 h the median SBAs for imipenem and meropenem, were 409 and 34.9 and 97.9 and 5.8, respectively, against Staphylococcus aureus, 19.9 and 4.4 and 19.4 and 4.8, respectively, against Pseudomonas aeruginosa, 34.3 and 2.2 and 232 and 15.5, respectively, against Enterobacter cloacae, and 13.4 and 2.25 and 90.7 and 7.9, respectively, against Proteus mirabilis. Both drugs had rather short biological elimination half-lives and a predominantly renal route of elimination. Both carbapenems revealed high SBAs against clinically important pathogens at 1 h; meropenem had a higher SBA against E. cloacae and P. mirabilis, and the SBA of imipenem against S. aureus was greater than the SBA of meropenem.

scholarly journals Pharmacokinetics of Intravenous Piperacillin Administration in Patients Undergoing On-Line Hemodiafiltration

2009 ◽  
Vol 53 (8) ◽  
pp. 3266-3268 ◽  
Author(s):  
Kook-Hwan Oh ◽  
Chiweon Kim ◽  
Hankyu Lee ◽  
Hajeong Lee ◽  
Ji Yong Jung ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Total Body Clearance ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Recovery Method ◽  
Elimination Half ◽  
On Line ◽  
The Mean ◽  
Total Body ◽  
Body Clearance

ABSTRACT The pharmacokinetic characteristics of piperacillin sodium were studied in five volunteers undergoing on-line hemodiafiltration (HDF). The subjects were given 2 g of piperacillin sodium intravenously over 1 min and placed on on-line HDF for 4 h starting at 60 min after the piperacillin infusion. Noncompartmental models were employed for estimation of the pharmacokinetic parameters, and intradialytic piperacillin clearance was calculated by the recovery method. The mean volume of distribution and the elimination half-life were 0.27 ± 0.13 liter/kg (mean ± standard deviation) and 1.1 ± 0.6 h, respectively. The total body clearance of piperacillin was 0.19 ± 0.08 liter/h/kg. Piperacillin clearance through on-line HDF was 0.11 ± 0.06 liter/h/kg. The mean serum piperacillin concentration was 4.0 ± 1.9 μg/ml at the end of the 4-h on-line HDF session. The concentration of infused piperacillin recovered in the dialysate was 527 ± 236 mg (26.3% ± 11.8%). We suggest the replacement of 500 mg of piperacillin after each on-line HDF session.

Pharmacokinetics of Once-Daily Ip Gentamicin in Capd Patients

1996 ◽  
Vol 16 (4) ◽  
pp. 379-384 ◽  
Author(s):  
Chai Luan Low ◽  
George R. Bailie ◽  
Anne Evans ◽  
George Eisele ◽  
Richard A. Venezia
Keyword(s):  
Renal Function ◽  
Open Study ◽  
Residual Renal Function ◽  
Volume Of Distribution ◽  
Peritoneal Membrane ◽  
Time Data ◽  
Once Daily ◽  
Concentration Time ◽  
Elimination Half ◽  
The Mean

Objective This study aimed to investigate the pharmacokinetic characteristics of once-daily intraperitoneal (IP) gentamicin in continuous ambulatory peritoneal dialysis (CAPD) patients. Design Prospective, nonrandomized, open study. Setting CAPD outpatient clinic in a teaching hospital. Patients Ten volunteer CAPD patients without peritonitis. Interventions Each patient received a single IP dose of 0.6 mg/kg of gentamicin. Blood and dialysate samples were collected at 0,0.5,1, 2, 3,6 (end of first dwell), and 24 hours after the administration of IP gentamicin. Any urine produced over the 24hour study period was also collected. The dialysate concentration/time data were fitted to a monoexponential curve for all patients. Results The bioavailability was 56±11% over a six hour dwell. The mean serum elimination half-life (t1/2) was 35.8 hours. The volume of distribution was 0.23±0.08 L/kg. Equilibration of gentamicin across the peritoneal membrane was rapid, with a t½ equilibration of 4.5 hours. The peritoneal clearance was 5.74±1.5 mL/min. Patients with residual renal function had significantly higher systemic gentamicin clearances (7.36±1.46 mL/min) than those of anuric patients (4.76±1.08 mL/min, p < 0.024). Conclusion Currently recommended doses of oncedaily IP gentamicin for the treatment of peritonitis may not produce the desired therapeutic serum and dialysate concentrations over 24 hours for effective treatment of peritonitis.

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