Decrease in Theophylline Clearance after the Administration of Erythromycin to a Patient with Obstructive Lung Disease

1983 ◽  
Vol 17 (5) ◽  
pp. 370-372 ◽  
Author(s):  
J.A. Green ◽  
W.A. Clementi
Keyword(s):  
Time Course ◽  
Total Body Clearance ◽  
Elevated Serum ◽  
Chronic Obstructive ◽  
Serum Theophylline ◽  
Obstructive Pulmonary Disease ◽  
Theophylline Disposition ◽  
Clinically Significant ◽  
Total Body ◽  
Body Clearance

It has been demonstrated previously that erythromycin can inhibit the total body clearance of theophylline, resulting in elevated serum theophylline concentrations. The overall incidence of this interaction and the population at risk have not been elucidated fully. Recent investigations have suggested that such an interaction is doubtful and that patients in whom this occurrence was suspect developed alterations in theophylline disposition secondary to worsening pulmonary function, not from erythromycin therapy alone. This case report shows that the interaction between theophylline and erythromycin can be clinically significant, producing as much as a 50-percent reduction in the total body clearance of the bronchodilator. The magnitude and time course of this interaction in patients with congestive heart failure and chronic obstructive pulmonary disease may differ considerably from that reported in healthy volunteers.

Disposition of Foscarnet during Peritoneal Dialysis

1996 ◽  
Vol 30 (10) ◽  
pp. 1106-1109 ◽  
Author(s):  
Alicia CM Alexander ◽  
Adam Akers ◽  
Gary R. Matzke ◽  
Francesca T. Aweeka ◽  
Donald S. Fraley
Keyword(s):  
Renal Function ◽  
Peritoneal Dialysis ◽  
Serum Concentration ◽  
Normal Renal Function ◽  
Half Life ◽  
Total Body Clearance ◽  
Case Summary ◽  
Clinically Significant ◽  
Total Body ◽  
Body Clearance

OBJECTIVE: To report the disposition of foscarnet in a patient undergoing peritoneal dialysis. CASE SUMMARY: A 34-year-old man with AIDS received foscarnet for the treatment of esophageal cytomegalovirus. We characterized the clearance of foscarnet in this patient during continuous cyclic peritoneal dialysis (CCPD) and continuous ambulatory peritoneal dialysis (CAPD). DISCUSSION: The foscarnet half-lives during CCPD and CAPD were 41.4 and 45.8 hours, respectively. These values are significantly greater than the half-life of 4.5 hours observed in patients with normal renal function and about half that reported in anuric patients undergoing hemodialysis during the interdialytic period. The CCPD and CAPD clearances of foscarnet were 5.8 and 4.5 mL/min, respectively; the CAPD clearances of creatinine and urea nitrogen were 4.1 and 6.0 mL/min, respectively. The patient's estimated total body clearance values of foscarnet during CCPD and CAPD were 9.8 and 8.8 mL/min, respectively. Thus, CCPD and CAPD augmented the patient's residual clearance of foscarnet by 145% and 105%, respectively. CONCLUSIONS: Since incremental increases in residual clearance of 30% or more generally will result in clinically significant changes in a drug's serum concentration, foscarnet dosage needs to be individualized for patients receiving peritoneal dialysis.

scholarly journals Pharmacokinetics of anti-infective agents during CytoSorb hemoadsorption

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Antoine G. Schneider ◽  
Pascal André ◽  
Joerg Scheier ◽  
Monika Schmidt ◽  
Heiko Ziervogel ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Total Body Clearance ◽  
Dosage Adjustment ◽  
Liposomal Amphotericin B ◽  
Beta Lactams ◽  
Significant Extent ◽  
Clinically Significant ◽  
Total Body ◽  
Body Clearance

AbstractCytokine hemoadsorption might be beneficial in patients with sepsis. However, its effect on anti-infective agents' disposition remains largely unknown. We sought to determine the influence of hemoadsorption on the pharmacokinetics of common anti-infective agents. This is an interventional experimental study, conducted in 24 healthy pigs. Animals were randomly allocated to either hemoadsorption (cases) or sham extracorporeal circuit (controls) and to drug combinations (3 cases and 3 controls for each combination). Hemoadsorption was performed with CytoSorb (CytoSorbents Corporation, USA). We evaluated 17 drugs (clindamycin, fluconazole, linezolid, meropenem, piperacillin, anidulafungin, ganciclovir, clarithromycin, posaconazole, teicoplanin, tobramycin, ceftriaxone, ciprofloxacin, metronidazole, liposomal amphotericin B, flucloxacillin and cefepime). Repeated blood sampling from the extracorporeal circulation (adsorber inlet/outlet, sham circuit) was performed over six hours following administration. Total clearance and adsorber-specific clearance were computed. Hemoadsorption was associated with increased clearance of all study drugs, except ganciclovir. Its impact on total body clearance was considered as moderate for fluconazole (282%) and linezolid (115%), mild for liposomal amphotericin B (75%), posaconazole (32%) and teicoplanine (31%) and negligible for all other drugs. Hemoadsorber clearance declined over time, with even delayed desorption for beta-lactams. It was moderately correlated with drug's lipophilicity (p = 0.01; r2 = 0.43). Hemoadsorption with CytoSorb appears to increase to a clinically significant extent the clearance of five among 17 tested anti-infectives. Studies in human patients are required to confirm the need for dosage adjustment of these agents.

scholarly journals Diagnostic performance of lung volumes in assessment of reversibility in chronic obstructive pulmonary disease

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Gamal Agmy ◽  
Manal A. Mahmoud ◽  
Azza Bahaa El-Din Ali ◽  
Mohamed Adam
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Cutoff Point ◽  
Whole Body ◽  
Significant Response ◽  
Chronic Obstructive ◽  
Lung Volumes ◽  
Obstructive Pulmonary Disease ◽  
Gold Stage ◽  
Clinically Significant

Abstract Background Reversibility measured by spirometry in chronic obstructive pulmonary disease (COPD) is defined as an increase in forced expiratory volume in first second (FEV1) that is both more than 12% and 200 mL above the pre-bronchodilator value in response to inhaled bronchodilators. FEV1 only may not fully reverberate the changes caused by reduction in air trapping or hyperinflation. To date, the studies that examined the effect of inhaled bronchodilators (BD) on residual volume (RV) and total lung capacity (TLC) are limited. This study was carried out to assess the differences between flow and volume responses after bronchodilator reversibility testing in patients with different COPD GOLD stages (GOLD stage I to stage IV). Spirometry and whole body plethysmography were done before and 15 min after inhalation of 400 μg salbutamol. Results Majority (53.3%) of cases were volume responders, 18.7% were flow responders, 20% were flow and volume responders, and 8% were non responders. Significant increase in Δ FEV1% was found in 15% of cases while 55% showed a significant increase in Δ FVC (P= < 0.001). Mean difference of Δ FVC (L) post BD was significantly increased with advancing GOLD stage (P= 0.03). A cutoff point > 20% for Δ RV% had 70% sensitivity and 60% specificity and > 12% for Δ TLC% showed 90% sensitivity and 45% specificity for prediction of clinically significant response to BD based on FEV1. A cutoff point > 18% for Δ RV% had 78% sensitivity and 29% specificity and > 14% for Δ TLC% had 50% sensitivity and 70% specificity for prediction of clinically significant response to BD based on FVC. Conclusion ΔFEV1 underestimates the true effect of bronchodilators with advancing GOLD stage. Measurement of lung volumes in addition to the standard spirometric indices is recommended when determining bronchodilator response in COPD patients.

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.

Hepatomesenteric release and removal of norepinephrine in swine

1995 ◽  
Vol 268 (4) ◽  
pp. R924-R930 ◽  
Author(s):  
A. Aneman ◽  
G. Eisenhofer ◽  
L. Fandriks ◽  
P. Friberg
Keyword(s):  
Total Body Clearance ◽  
Splanchnic Nerve ◽  
Neuronal Uptake ◽  
Blocking Drug ◽  
Hepatic Extraction ◽  
Valid Assessment ◽  
Total Body ◽  
Splanchnic Nerve Stimulation ◽  
Body Clearance ◽  
Venous Plasma

Release and removal of norepinephrine (NE) by hepatomesenteric organs in anesthetized swine were examined using measurements of NE in arterial, portal, and hepatic venous plasma. NE spillover from the liver and mesenteric organs increased during splanchnic nerve stimulation, validating these measurements as indexes of sympathetic outflow. Administration of the neuronal uptake-blocking drug desipramine reduced mesenteric NE extraction more than hepatic extraction, suggesting that neuronal uptake was more important for NE removal in mesenteric organs than in the liver. Circulating NE was removed by the liver more efficiently than by mesenteric organs, whereas mesenteric NE spillover (2.46 nmol/min) exceeded liver NE spillover (0.74 nmol/min). Hepatomesenteric NE spillover represented 53% of total body spillover; NE clearance was 42% of total body clearance. Because of efficient hepatic extraction of NE released by mesenteric organs, the sum of mesenteric and hepatic NE spillovers (3.20 pmol/min) exceeded net hepatomesenteric spillover estimated using arterial and hepatic venous measurements alone (1.96 pmol/min). Thus valid assessment of the substantial amounts of NE released by hepatomesenteric organs requires separate examination of mesenteric and hepatic spillovers.

scholarly journals β-Lactam Dosage Regimens in Septic Patients with Augmented Renal Clearance

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Alexandra Jacobs ◽  
Fabio Silvio Taccone ◽  
Jason A. Roberts ◽  
Frédérique Jacobs ◽  
Frederic Cotton ◽  
...  
Keyword(s):  
Creatinine Clearance ◽  
Renal Clearance ◽  
Total Body Clearance ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Augmented Renal Clearance ◽  
Drug Concentrations ◽  
Trough Concentrations ◽  
Total Body ◽  
Body Clearance

ABSTRACTAugmented renal clearance is commonly observed in septic patients and may result in insufficient β-lactam serum concentrations. The aims of this study were to evaluate potential correlations between drug concentrations or total body clearance of β-lactam antibiotics and measured creatinine clearance and to quantify the need for drug dosage adjustments in septic patients with different levels of augmented renal clearance. We reviewed 256 antibiotic measurements (512 drug concentrations) from a cohort of 215 critically ill patients who had a measured creatinine clearance of ≥120 ml/min and who received therapeutic drug monitoring of meropenem, cefepime, ceftazidime, or piperacillin from October 2009 until December 2014 at Erasme Hospital. Population pharmacokinetic (PK) analysis of the data was performed using the Pmetrics software package for R. Fifty-five percent of drug concentrations showed insufficient β-lactam serum concentrations to treat infections due toPseudomonas aeruginosa. There were significant, yet weak, correlations between measured creatinine clearance and trough concentrations of meropenem (r= −0.21,P= 0.01), trough concentrations of piperacillin (r= −0.28,P= 0.0071), concentrations at 50% of the dosage interval (r= −0.41,P< 0.0001), and total body clearance of piperacillin (r= 0.39,P= 0.0002). Measured creatinine clearance adequately explained changes in drug concentrations in population pharmacokinetic models for cefepime, ceftazidime, and meropenem but not for piperacillin. Therefore, specific PK modeling can predict certain β-lactam concentrations based on renal function but not on absolute values of measured creatinine clearance, easily available for clinicians. Currently, routine therapeutic drug monitoring is required to adjust daily regimens in critically ill patients receiving standard dosing regimens.

Human plasma pharmacokinetics of thiotepa following administration of high-dose thiotepa and cyclophosphamide.

1988 ◽  
Vol 6 (7) ◽  
pp. 1192-1196 ◽  
Author(s):  
S P Ackland ◽  
K E Choi ◽  
M J Ratain ◽  
M J Egorin ◽  
S F Williams ◽  
...  
Keyword(s):  
Stepwise Regression ◽  
Total Body Clearance ◽  
Linear Functions ◽  
High Dose ◽  
Metabolic Clearance ◽  
Plasma Decay ◽  
Plasma Pharmacokinetics ◽  
Total Body ◽  
Dose Dependent ◽  
Body Clearance

Thiotepa is an established alkylating agent whose pharmacokinetics in standard doses are well defined. In order to ascertain whether dose-dependent variations in pharmacokinetics occur, we have undertaken an analysis of plasma thiotepa levels in 16 patients entered on a phase I-II study of bialkylator chemotherapy. High-dose thiotepa (1.8 to 7.0 mg/kg) and cyclophosphamide (2.5 g/m2) were administered intravenously (IV) on days -6, -4, and -2 followed by autologous marrow reinfusion on day 0. Plasma and urinary thiotepa was assayed by gas chromatography. Biexponential plasma decay curves were seen in ten patients, with a t 1/2 alpha of 10.0 +/- 6.4 minutes, a t 1/2 beta of 174 +/- 61 minutes and a total body clearance of 379 +/- 153 mL/h/kg (mean +/- SD). Six patients displayed monoexponential plasma decay curves with a terminal t 1/2 of 137 +/- 83 minutes and a total body clearance of 440 +/- 195 mL/h/kg. Although there was a trend toward reduced plasma clearance in the three patients treated at the highest dose level, the available data suggest that metabolic clearance mechanisms for thiotepa were not saturated with the doses used in this study. By stepwise regression analysis, linear functions using only 15-minute and four-hour postinfusion plasma levels were derived that correlated closely with area under the plasma concentration X time curves (AUC) (P less than .002). We conclude that high-dose thiotepa results in similar pharmacokinetic values to conventional doses with no apparent dose-dependent variation. The value of specific time points to predict AUC and clearance will require prospective evaluation.

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