scholarly journals Enhanced renal clearance and impact on vancomycin pharmacokinetic parameters in patients with hemorrhagic stroke

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Kathryn A. Morbitzer ◽  
Denise H. Rhoney ◽  
Kelly A. Dehne ◽  
J. Dedrick Jordan
Keyword(s):  
Renal Clearance ◽  
Half Life ◽  
Hemorrhagic Stroke ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Elimination Rate ◽  
Pharmacokinetic Parameters ◽  
The Mean ◽  
A Prospective Study ◽  
Post Hoc ◽  
The Impact

Abstract Background The majority of patients with hemorrhagic stroke experience enhanced renal clearance or augmented renal clearance (ARC). The purpose of this study was to determine the impact of enhanced renal clearance or ARC on vancomycin pharmacokinetic (PK) parameters. Methods This was a post hoc analysis of a prospective study of adult patients with aneurysmal subarachnoid hemorrhage (aSAH) or intracerebral hemorrhage (ICH) admitted to the neurosciences intensive care unit who received vancomycin. Creatinine clearance (CrCl) was measured and also estimated using the Cockcroft-Gault equation. Predicted PK parameters were compared with calculated PK parameters using serum peak and trough concentrations. Results Seventeen hemorrhagic stroke patients met inclusion criteria. All patients experienced enhanced renal clearance on the day that the vancomycin concentrations were obtained, and 12 patients (71%) experienced ARC. The mean calculated elimination rate constant was significantly higher than the predicted value (0.141 ± 0.02 vs. 0.087 ± 0.01 h−1; p = 0.004) and the mean calculated half-life was significantly lower than the predicted half-life (6.5 ± 0.9 vs. 8.7 ± 0.6 h; p = 0.03). Conclusions Patients with hemorrhagic stroke and enhanced renal clearance displayed PK alterations favoring an increased elimination of vancomycin than expected. This may result in underexposure to vancomycin, leading to treatment failure.

Pharmacokinetics of Intermittent Intraperitoneal Cefazolin in Continuous Ambulatory Peritoneal Dialysis Patients

1999 ◽  
Vol 19 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Harold J. Manley ◽  
George R. Bailie ◽  
Rupesh D. Asher ◽  
George Eisele ◽  
Reginald F. Frye
Keyword(s):  
Body Weight ◽  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Rate Constant ◽  
Half Life ◽  
Elimination Rate ◽  
Pharmacokinetic Parameters ◽  
Number Of Patients ◽  
The Mean ◽  
Concentration Levels

Objective To investigate the pharmacokinetic parameters of intermittent intraperitoneal (IP) cefazolin, and recommend a cefazolin dosing regimen in continuous ambulatory peritoneal dialysis (CAPD) patients. Design Prospective nonrandomized open study. Setting CAPD outpatient clinic in Albany, New York. Patients Seven volunteer CAPD patients without peritonitis. Three of the patients were nonanuric while 4 were anuric. Interventions Cefazolin (15 mg/kg total body weight) was given to each patient during the first peritoneal exchange. Blood and dialysate samples were collected at times 0, 0.5, 1, 2, 3, 6 (end of the first antibiotic-containing dwell), 24, and 48 hours after the administration of IP cefazolin. Urine samples were collected in nonanuric patients over the study period. Results The mean ± SD amount of cefazolin dose absorbed from the dialysate after the 6-hour dwell was 69.7% ± 8.0% of the administered dose. The cefazolin absorption rate constant from dialysate to serum was 0.21 ± 0.1 /hr (absorption half-life 3.5 ± 0.8 hr). The mean serum concentrations reached at 24 and 48 hours were 52.4 ± 3.7 mg/L and 30.3 ± 5.9 mg/L, respectively. The mean dialysate cefazolin concentrations reached at 24 and 48 hours were 15.1 ± 3.4 mg/L and 7.9 ± 1.4 mg/L, respectively. The cefazolin serum elimination rate constant was 0.02 ± 0.01 /hr (elimination half-life 31.5 ± 8.8 hr). The total cefazolin body clearance was 3.4 ± 0.6 mL/min. In the 3 nonanuric patients the mean renal clearance of cefazolin was 0.6 ± 0.4 mL/min. The peritoneal clearance of cefazolin was 1.0 ± 0.3 mL/min. The systemic volume of distribution of cefazolin was 0.2 ± 0.05 L/kg. No statistical difference was detected in pharmacokinetic parameters between anuric and nonanuric patients, although this may be due to the small number of patients in each group. Conclusion A single daily dose of cefazolin dosed at 15 mg/kg actual body weight in CAPD patients is effective in achieving serum concentration levels greater than the minimum inhibitory concentration for sensitive organisms over 48 hours, and dialysate concentration levels over 24 hours. Caution is warranted in extrapolation of dosing recommendations to patients who maintain a significant degree of residual renal function.

scholarly journals hCGbeta core fragment is a metabolite of hCG: evidence from infusion of recombinant hCG

2000 ◽  
Vol 164 (3) ◽  
pp. 299-305 ◽  
Author(s):  
RJ Norman ◽  
MM Buchholz ◽  
AA Somogyi ◽  
F Amato
Keyword(s):  
Renal Clearance ◽  
Clearance Rate ◽  
Half Life ◽  
Urine Samples ◽  
Molar Ratio ◽  
Gel Chromatography ◽  
Core Fragment ◽  
Terminal Half Life ◽  
Intact Molecule ◽  
The Mean

The availability of recombinant human chorionic gonadotrophin (r-hCG) has allowed us to measure its metabolic and renal clearance rates and to study the origin of the beta core fragment of hCG (hCGbetacf). Serum and urine samples were collected from six subjects, after an intravenous injection of 2 mg (equivalent to 44 000 IU Urinary hCG) r-hCG, and assayed for hCG and the beta subunit (hCGbeta). Urine from four of the subjects was also subjected to gel chromatography and assayed for hCGbetacf and hCG. r-hCG, administered as an intravenous dose, was distributed, initially in a volume of 3.4+/-0.7 l (mean+/-s.d.) and then in 6.5+/-1.15 l at steady-state. The disappearance of r-hCG from serum was bi-exponential, with an initial half-life of 4.5+/-0.7 h and a terminal half-life of 29.0+/-4.6 h. The mean residence time was 28. 6+/- 3.6 h and the total systemic clearance rate of r-hCG was 226+/-18 ml/h. The renal clearance rate was 28.75+/-6.2 ml/h (mean+/-s.d). hCGbetacf was detected in all urine samples collected at 6 h intervals. Over the 138 h period of urine collection, 12.9% (range 10.1-17.3% ) of r-hCG injected was recovered as the intact molecule and 1.7% (range 0.8-2.9%) was recovered as the hCGbetacf, in 4 subjects. The molar ratio of hCGbetacf to hCG in urine increased from 3.1+/-1.7%, on day 1, to 76+/-34.3% (mean+/-s.e.m.) on day 5, after r-hCG infusion, suggesting that hCGbetacf is a metabolic product of the infused r-hCG.

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.

Propranolol Plasma Concentrations and Plasmapheresis

1981 ◽  
Vol 15 (12) ◽  
pp. 993-996 ◽  
Author(s):  
Robert L. Talbert ◽  
Yan Yan Wong ◽  
Douglas B. Duncan
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Rate Constant ◽  
Half Life ◽  
Plasma Concentrations ◽  
Elimination Rate ◽  
Elimination Rate Constant ◽  
Before And After ◽  
Uremic Syndrome ◽  
The Mean

Propranolol plasma concentrations were determined in a patient with hemolytic-uremic syndrome undergoing plasmapheresis before and after the procedure on three occasions. The mean half-life and elimination rate constant during plasmapheresis were estimated to be 25.6 percent of the values obtained without plasmapheresis. These changes suggest that plasmapheresis may influence propranolol disposition.

scholarly journals Microcephaly Outcomes among Zika Virus–Infected Pregnant Women in Honduras

2021 ◽  
Author(s):  
Jackeline Alger ◽  
Pierre Buekens ◽  
Maria Luisa Cafferata ◽  
Zulma Alvarez ◽  
Mabel Berrueta ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Head Circumference ◽  
Zika Virus ◽  
Regional Variation ◽  
Serum Samples ◽  
Zikv Infection ◽  
Prenatal Visit ◽  
The Mean ◽  
A Prospective Study ◽  
The Impact

The impact of Zika virus (ZIKV) infection on pregnancies shows regional variation emphasizing the importance of studies in different geographical areas. We conducted a prospective study in Tegucigalpa, Honduras, recruiting 668 pregnant women between July 20, 2016, and December 31, 2016. We performed Trioplex real-time reverse transcriptase–PCR (rRT-PCR) in 357 serum samples taken at the first prenatal visit. The presence of ZIKV was confirmed in seven pregnancies (7/357, 2.0%). Nine babies (1.6%) had microcephaly (head circumference more than two SDs below the mean), including two (0.3%) with severe microcephaly (head circumference [HC] more than three SDs below the mean). The mothers of both babies with severe microcephaly had evidence of ZIKV infection. A positive ZIKV Trioplex rRT-PCR was associated with a 33.3% (95% CI: 4.3–77.7%) risk of HC more than three SDs below the mean.

scholarly journals Impact of increasing dialysis volume on adequacy targets: a prospective study.

1997 ◽  
Vol 8 (8) ◽  
pp. 1304-1310 ◽  
Author(s):  
J Harty ◽  
H Boulton ◽  
M Venning ◽  
R Gokal
Keyword(s):  
Renal Function ◽  
Peritoneal Dialysis ◽  
Prospective Study ◽  
Creatinine Clearance ◽  
Renal Clearance ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Target Values ◽  
A Prospective Study ◽  
The Impact ◽  
Solute Clearance

Failure to achieve target values for both urea (Kt/V) and creatinine clearance has been associated with increased morbidity and mortality in continuous ambulatory peritoneal dialysis patients. The conventional continuous ambulatory peritoneal dialysis regimen, which uses four 2-L exchanges per day, has resulted in up to 40% of such patients failing to achieve proposed targets for weekly Kt/V of 1.7 and weekly creatinine clearance (WCC) of 50 L. In a prospective study, the impact of increasing prescribed volumes by 0.5 L per exchange was evaluated on attaining urea and creatinine clearance targets over a 1-yr period. At 1 yr, 17 patients remaining on the increased dialysis prescription were compared with 18 patients remaining on an unchanged regimen. The mean increase in daily prescribed volume was 1.5 L (22%). This resulted in a significant increase in both peritoneal dialysis Kt/V (1.59 to 1.78 L = 12%) and peritoneal dialysis WCC (45.8 to 50.1 L = 10%) by 1 yr. Because of loss of renal function, there was no significant increase in total clearance at 1 yr, but this loss of renal clearance was offset by the gain in peritoneal clearance. Residual renal function fell at a similar rate in both the increased dialysis and control groups. In the latter, although peritoneal clearance remained stable over the 1-yr period, loss of renal function resulted in reductions in both total Kt/V and WCC. In conclusion, exchange volume can be increased to compensate for loss of renal function over a 1-yr period. Progressive loss of renal clearance resulted in only a modest gain in total solute clearance. It was the larger patients who tolerated the increase in exchange volumes. However, such patients (by virtue of their size) tended not to achieve target values for solute clearance, and the modest gain in peritoneal clearance was insufficient to increase the number of patients in this group achieving such targets for dialysis adequacy.

P–663 The ratio of serum progesterone (P4) to the number of follicles (P4/Follicle) is a more objective parameter for euploidy rate as compared to systemic progesterone

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
K Ab. ali ◽  
B Lawrenz ◽  
A L Tegedor ◽  
F R Ruiz ◽  
A El-Damen ◽  
...  
Keyword(s):  
Oocyte Maturation ◽  
Ovarian Stimulation ◽  
Follicular Phase ◽  
Preimplantation Genetic Testing ◽  
Serum Progesterone ◽  
Final Oocyte Maturation ◽  
The Mean ◽  
A Prospective Study ◽  
The Impact ◽  
Ploidy Status

Abstract Study question Does the ratio of serum progesterone (P4) to the number of follicles (P4/Follicle) on the day of final oocyte maturation affect the ploidy status of the embryos? Summary answer A high P4/Follicle ratio negatively affects the euploid rate of the embryos. What is known already During ovarian stimulation, exogenous gonadotropins are administered to achieve multifollicular growth. Intense gonadotropin stimulation towards the end of the follicular phase seems to cause a premature progesterone rise in stimulated IVF cycles. The impact of serum progesterone elevation during the follicular phase has been studied intensively. Though most studies have focused on the effect of progesterone elevation on the endometrial receptivity, little is known about its possible impact on embryo development and ploidy status. The only study that investigated the effect of progesterone on the embryo ploidy status, was unable to show any significant impact. Study design, size, duration This retrospective study was performed at ART Fertility Clinics Abu Dhabi, UAE and Muscat, Oman. All stimulation cycles (n = 975) were performed between January 2015 to December 2019 with patients aged between 18–45, Body mass index (BMI) of 18–35, stimulated either with rFSH or hMG. All embryos underwent ICSI and Preimplantation Genetic Testing for Aneuploidies (PGT-A),Patients with surgical sperm extraction, warmed oocytes or natural cycle IVF were excluded. Participants/materials, setting, methods Serum P4 was measured on the last ultrasound prior triggering for final oocyte maturation. The P4/Follicle ratio was calculated as the ratio of P4 on trigger day to the number of follicles > 10 mm on the last ultrasound. Serum P4 and P4/Follicle ratio were then analyzed using linear and univariate regression model to find potential correlation with the number of oocytes retrieved, number of mature oocytes, embryo quality (day 3 and 5), and euploid rate. Main results and the role of chance A total of 975 cycles were analyzed, with a mean age of 33.88±0.05 years, a mean BMI of 26.7±0.035 kg/m2. The mean number of oocytes collected was 12.53±0.058. Mean serum P4 on trigger day was 0.83±0.005 ng/ml and higher serum P4 values were observed as the number of oocytes retrieved and the number of mature oocytes increased (β = 0.026, p < 0.0001 and β = 0.028, p < 0.001, respectively). On the other hand, the mean P4/Follicle ratio was 0.056±0.00041 ng/ml and, unlike serum P4, the P4/Follicle ratio showed a negative correlation with the number of oocytes retrieved as well as with the number of mature oocytes (β=–0.001, p < 0.001 and β=–0.001, p < 0.001, respectively). While day 3 embryos were not affected by serum P4 or P4/Follicle ratio, the blastocyst quality was negatively affected by both increasing serum P4 levels and the P4/Follicle ratio (β=–0.012 p < 0.05, β=–0.002, p < 0.001, respectively). Euploid rates were positively correlated in cycles with increased serum P4 β = 0.18, p < 0.001), while negatively correlated in cycles with a high P4/Follicle ratio (β=–0.015, p < 0.001). After adjusting for potential confounders, only P4/Follicle remained as a significant negative factor for euploid rate (β=–0.004, p < 0.001, 95% CI: –0.007- –0.001, p < 0.001), which was not observed for serum P4 (p = 0.46). Limitations, reasons for caution This is an observational study based on retrospective data; an improved extrapolation of the results might be obtained by performing a prospective study. Wider implications of the findings: The findings of this study should encourage clinicians to optimize the ovarian stimulation protocols not only based on serum P4, but also considering the P4/Follicle ratio. Trial registration number Not applicable

scholarly journals Antimullerian Hormone Changes after Laparoscopic Ovarian Cystectomy for Endometrioma Compared with the Nonovarian Conditions

2014 ◽  
Vol 2014 ◽  
pp. 1-5
Author(s):  
Chamnan Tanprasertkul ◽  
Sakol Manusook ◽  
Charintip Somprasit ◽  
Sophapun Ekarattanawong ◽  
Opas Sreshthaputra ◽  
...  
Keyword(s):  
Ovarian Reserve ◽  
Negative Impact ◽  
Pelvic Surgery ◽  
Ovarian Cystectomy ◽  
Antimullerian Hormone ◽  
Significant Difference ◽  
The Mean ◽  
Antimüllerian Hormone ◽  
A Prospective Study ◽  
The Impact

Laparoscopic ovarian cystectomy is recommended for surgical procedure of endometrioma. The negative impact on ovarian reserve following removal had been documented. Little evidence had been reported for nonovarian originated effects.Objective.To evaluate the impact of laparoscopic ovarian cystectomy for endometrioma on ovarian reserve, measured by serum antimullerian hormone (AMH), compared to nonovarian pelvic surgery.Materials and Methods.A prospective study was conducted. Women who underwent laparoscopic ovarian cystectomy (LOC) and laparoscopic nonovarian pelvic surgery (NOS) were recruited and followed up through 6 months. Clinical baseline data and AMH were evaluated.Results.39 and 38 participants were enrolled in LOC and NOS groups, respectively. Baseline characteristics (age, weight, BMI, and height) and preoperative AMH level between 2 groups were not statistically different. After surgery, AMH of both groups decreased since the first week, at 1 month and at 3 months. However, as compared to the LOC group at 6 months after operation, the mean AMH of the NOS group had regained its value with a highly significant difference.Conclusion.This study demonstrated the negative impact of nonovarian or indirect effects of laparoscopic surgery to ovarian reserve. The possible mechanisms are necessary for more investigations.

Gentamicin Pharmacokinetics in Elderly Patients with Normal Renal Function

1994 ◽  
Vol 10 (1) ◽  
pp. 14-17 ◽  
Author(s):  
Ji M. Koo ◽  
Donald R. Miller ◽  
Charles D. Peterson
Keyword(s):  
Renal Function ◽  
Elderly Patients ◽  
Normal Renal Function ◽  
Medical Center ◽  
Elimination Rate ◽  
The Elderly ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Trough Concentrations ◽  
The Mean

Objective: To establish the pharmacokinetic parameters of gentamicin in elderly patients and to compare predicted concentrations based on the Dettli method, with actual concentrations. Design: Measurement of gentamicin concentrations and pharmacokinetic parameters in a consecutive patient sample with comparison to ones predicted by the Dettli method. Setting: Medical and surgical units in a Veterans Affairs Medical Center. Patients: Forty-six consecutive elderly men treated with gentamicin for documented or presumed infection and had stable, normal renal function. Main Outcome Measures: The following information was calculated or measured: elimination rate constant (kel), elimination half-life, volume of distribution (Vd), and peak and trough concentrations. Results: The mean kel (0.16 ± 0.05 h−1) was not significantly different (p=0.2) from the Dettli method prediction, and the mean Vd (0.36 ± 0.1 L/kg) was 37 percent higher than that usually reported. Actual peak and trough concentrations were significantly lower (both p<0.01) than predicted concentrations. Conclusions: Based on our findings, higher than recommended loading doses and longer dosage intervals may be required in the elderly. The Dettli method is useful to estimate kel in the elderly.

scholarly journals Absorption and Elimination of Oat Avenanthramides in Humans after Acute Consumption of Oat Cookies

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Tianou Zhang ◽  
Jing Shao ◽  
Yike Gao ◽  
Chi Chen ◽  
Dan Yao ◽  
...  
Keyword(s):  
Half Life ◽  
Plasma Concentrations ◽  
Elimination Rate ◽  
Pharmacokinetic Parameters ◽  
Oral Ingestion ◽  
Blood Samples ◽  
Oral Consumption ◽  
Maximal Plasma ◽  
Oat Flour ◽  
Antioxidant Effects

Background. Avenanthramides (AVA) are a group of diphenolic acids found only in oats that have anti-inflammatory and antioxidant effects. Absorption of AVAs in humans after oral consumption of natural oat flour is unknown.Objective. To examine the appearance of AVAs in plasma after oral ingestion of oat cookies and estimate key pharmacokinetic parameters.Methods. Male and female nonobese participants (n=16) consumed three cookies made with oat flour containing high (229.6 mg/kg, H-AVA) or low (32.7 mg/kg, L-AVA) amounts of AVAs, including AVA-A, AVA-B, and AVA-C. Blood samples were collected at 0, 0.5, 1, 2, 3, 5, and 10 h after ingestion. Plasma total (conjugated and free) AVA concentrations were quantified using UPLC-MS, and pharmacokinetic parameters for each AVA were estimated.Results. AVAs reached peak concentrations in plasma between 2 and 3 h for the H-AVA group and between 1 and 2 h for the L-AVA group. Maximal plasma concentrations for AVAs were higher in the H-AVA than in the L-AVA group. AVA-B demonstrated a longer half-life and slower elimination rate than AVA-A and AVA-C.Conclusions. AVAs found naturally in oats are absorbed in the plasma after oral administration in humans. AVA-B has the slowest elimination rate and the longest half-life compared to AVA-A and AVA-C, while AVA-C demonstrated the lowest plasma concentrations. This study is registered with ClinicalTrials.gov identifierNCT02415374.

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