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.

Disposition of Deracoxib in Cats After Oral Administration

2006 ◽  
Vol 42 (3) ◽  
pp. 212-217 ◽  
Author(s):  
Adam D. Gassel ◽  
Karen M. Tobias ◽  
Sherry K. Cox
Keyword(s):  
Adverse Effects ◽  
Oral Administration ◽  
Drug Administration ◽  
Half Life ◽  
Maximum Concentration ◽  
Efficacy And Safety ◽  
Terminal Half Life ◽  
The Mean ◽  
Chronic Use

The pharmacokinetics of deracoxib in seven healthy cats were determined following a single oral (1 mg/kg) dose. Minimal variability among cats was found for all estimated pharmacokinetic variables. Terminal half-life (t1/2) was 7.9 hours. The mean maximum concentration (Cmax) was 0.28 μg/mL and was measured 3.64 hours after drug administration. Deracoxib was not detectable in the plasma after 60 hours. The compounded liquid formula was accepted readily, and no adverse effects were observed. Further studies are needed to determine the efficacy and safety of deracoxib after acute and chronic use in the cat.

scholarly journals Pharmacokinetics of Novel Erythropoiesis Stimulating Protein Compared with Epoetin Alfa in Dialysis Patients

1999 ◽  
Vol 10 (11) ◽  
pp. 2392-2395 ◽  
Author(s):  
IAIN C. MACDOUGALL ◽  
STEPHEN J. GRAY ◽  
ORLAITH ELSTON ◽  
CORMAC BREEN ◽  
BARBARA JENKINS ◽  
...  
Keyword(s):  
Single Dose ◽  
Half Life ◽  
Epoetin Alfa ◽  
Dialysis Patients ◽  
Open Label ◽  
Double Blind ◽  
Time Curve ◽  
Peptide Mass ◽  
Terminal Half Life ◽  
The Mean

Abstract. Novel erythropoiesis stimulating protein (NESP) is a hyperglycosylated analogue of recombinant human erythropoietin (Epoetin) which has an increased terminal half-life in animal models. The aim of this study was to extend these observations to humans. Using a double-blind, randomized, cross-over design, the single-dose pharmacokinetics of Epoetin alfa (100 U/kg) and an equivalent peptide mass of NESP were compared following intravenous bolus in 11 stable peritoneal dialysis patients. This was followed by an open-label study to determine the single-dose pharmacokinetics of an equivalent peptide mass of NESP by subcutaneous injection in six of these patients. The mean terminal half-life for intravenous NESP was threefold longer than for intravenous Epoetin (25.3 versus 8.5 h), a difference of 16.8 h (95% confidence interval, 9.4 to 24.2 h, P = 0.0008). The area under the serum concentration—time curve was significantly greater for NESP (291.0 ± 7.6 ng · h per ml versus 131.9 ± 8.3 ng · h per ml; mean ± SEM; P < 0.0005), and clearance was significantly lower (1.6 ± 0.3 ml/h per kg versus 4.0 ± 0.3 ml/h per kg; mean ± SEM; P < 0.0005). The volume of distribution was similar for NESP and Epoetin (52.4 ± 2.0 ml/kg versus 48.7 ± 2.1 ml/kg; mean ± SEM). The mean terminal half-life for subcutaneous NESP was 48.8 h. The peak concentration of subcutaneous NESP was approximately 10% of that following intravenous administration, and bioavailability was approximately 37% by the subcutaneous route. The longer half-life of NESP is likely to confer a clinical advantage over Epoetin by allowing less frequent dosing in patients treated for anemia.

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.

Elimination of Porcine Secretin in Pigs

1978 ◽  
Vol 54 (1) ◽  
pp. 61-68
Author(s):  
J. Fahrenkrug ◽  
O. B. Schaffalitzky de Muckadell ◽  
J. J. Holst
Keyword(s):  
Whole Blood ◽  
Clearance Rate ◽  
Intravenous Infusion ◽  
Half Life ◽  
Metabolic Clearance ◽  
Distribution Space ◽  
Metabolic Clearance Rate ◽  
The Mean ◽  
Arteriovenous Difference

1. The elimination of immunoreactive secretin was studied in anaesthetized pigs by using constant infusions of pure natural porcine secretin. 2. The mean metabolic clearance rate was 15·4 ml min—1 kg—1, and was independent of the level at which it was determined. The mean distribution space was 64·4 ml/kg. The half-life of secretin after termination of the infusion averaged 2·6 min. 3. During intravenous infusion of secretin in a dose of 27·8 pmol h—1 kg—1 the renal extraction was 52%. Exclusion of the kidneys increased plasma secretin concentration from 26·5 pmol/l to 47·3 pmol/l and increased the half-life to 4·4 min. 4. Exclusion of the liver during infusion of secretin in a dose of 27·8 pmol h—1 kg—1 resulted in an increment in plasma secretin concentration of 7·8 pmol/l and an increase of the half-life to 3·6 min. 5. A gradient of endogenous secretin across the liver was present but no arteriovenous difference was found across the foreleg. 6. Incubation of secretin with whole blood or serum for 20 min at 37°C did not result in any degradation of secretin.

Plasma Thrombospondin as an Indicator of Intravascular Platelet Activation in Patients with Vasculitis

1987 ◽  
Vol 58 (03) ◽  
pp. 850-852 ◽  
Author(s):  
M B McCrohan ◽  
S W Huang ◽  
J W Sleasman ◽  
P A Klein ◽  
K J Kao
Keyword(s):  
Platelet Activation ◽  
Plasma Levels ◽  
Half Life ◽  
Degradation Products ◽  
Plasma Concentrations ◽  
Primary Source ◽  
Positive Correlation ◽  
Activation Marker ◽  
Fibrin Degradation Products ◽  
The Mean

SummaryThe use of plasma thrombospondin (TSP) concentration was investigated as an indicator of intravascular platelet activation. Patients (n = 20) with diseases that have known vasculitis were included in the study. The range and the mean of plasma TSP concentrations of patients with vasculitis were 117 ng/ml to 6500 ng/ml and 791±1412 ng/ml (mean ± SD); the range and the mean of plasma TSP concentrations of control individuals (n = 33) were 13 ng/ml to 137 ng/ml and 59±29 ng/ml. When plasma TSP concentrations were correlated with plasma concentrations of another platelet activation marker, β-thromboglobulin (P-TG), it was found that the TSP concentration inei eased exponentially as the plasma β-TG level rose. A positive correlation between plasma levels of plasma TSP and serum fibrin degradation products was also observed. The results suggest that platelets are the primary source of plasma TSP in patients with various vasculitis and that plasma TSP can be a better indicator than β-TG to assess intravascular platelet activation due to its longer circulation half life.

HYPEROESTROGENISMUS AND RHEUMATOID ARTHRITIS

1960 ◽  
Vol XXXIV (I) ◽  
pp. 45-50 ◽  
Author(s):  
J. L. Kalliomäki ◽  
Lauri Rauramo
Keyword(s):  
Rheumatoid Arthritis ◽  
Cervical Cancer ◽  
Urine Samples ◽  
Menstrual Bleeding ◽  
Menstrual Phase ◽  
Joint Symptoms ◽  
The Mean

ABSTRACT The authors have endeavoured to clarify the frequency of the hyperoestrogenismus syndrome in women with rheumatoid arthritis, aged 17–38 years, by means of clinical and cytologic studies, and by hormonal analyses. The material comprises 32 patients. Of these, 30 were suitable for cytologic observation. In 5 (17 %) of these 30 patients, the hyperoestrogenismus syndrome (17 %) may be considered definitely established. Aggravation of the joint symptoms in the pre-menstrual phase was reported by 41 % of the patients. Values for excretion of oestrogen exceeding 200 mouse units/24 hours were noted one week before menstrual bleeding in 8 of 19 women; the mean for oestrogen excretion was 268 mouse units/24 hours. Gonadotrophins were studied in the same urine samples, and the mean excretion was 22 mouse units/24 hours (range 7–65 m. u.). The excretion mean for 17-ketosteroids, simultaneously studied, was 9.1 mg/24 hours (range 2.3–18.0 mg). Side-finding in the material were made: incipient cervical cancer in one patient, ovarial tumour in one, and trichomoniasis in seven.

Comparative metabolic clearance rate, volume of distribution and plasma half-life of human β-lipotropin and acth

Life Sciences ◽  
1978 ◽  
Vol 23 (23) ◽  
pp. 2323-2330 ◽  
Author(s):  
Anthony S. Liotta ◽  
Choh Hao Li ◽  
George C. Schussler ◽  
Dorothy T. Krieger
Keyword(s):  
Clearance Rate ◽  
Half Life ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Half Life

Phase I Dose-Finding Study of Weekly Single-Agent Patupilone in Patients With Advanced Solid Tumors

2005 ◽  
Vol 23 (36) ◽  
pp. 9120-9129 ◽  
Author(s):  
Eric H. Rubin ◽  
John Rothermel ◽  
Fisseha Tesfaye ◽  
Tianling Chen ◽  
Martine Hubert ◽  
...  
Keyword(s):  
Partial Response ◽  
Solid Tumors ◽  
Half Life ◽  
Drug Exposure ◽  
Dose Range ◽  
Single Agent ◽  
Dose Finding ◽  
Advanced Solid Tumors ◽  
Blood Concentrations ◽  
Terminal Half Life

Purpose To evaluate the safety and maximum-tolerated dose (MTD) of weekly patupilone, a natural epothilone B, in patients with advanced solid tumors. Patients and Methods Patients were treated with patupilone (0.3 to 3.6 mg/m2) for 6 weeks on/3 weeks off or 3 weeks on/1 week off. Dose-limiting toxicities (DLTs), MTD, and pharmacokinetics were determined for each schedule of administration. Results Ninety-one patients were enrolled. The most common tumor types included ovarian, breast, and colon cancers. Doses of patupilone less than 2.5 mg/m2 using either the 6 weeks on/3 weeks off or the 3 weeks on/1 week off schedule were tolerated well. At higher doses, DLTs were observed using both dosing schedules, with diarrhea the most common DLT. The MTD for both treatment schedules was 2.5 mg/m2. After a short infusion, patupilone blood concentrations declined in a multiphasic manner with a terminal half-life of 4 days. Drug clearance was nonrenal and was not related to body-surface area. Over the dose range evaluated, systemic drug exposure was approximately dose proportional. Three patients achieved a partial response, and 31 patients had stable disease. Two patients experiencing a partial response had received prior taxane therapy. Conclusion Patupilone is well tolerated when administered at a dose of 2.5 mg/m2, using either a 6 weeks on/3 weeks off or a 3 weeks on/1 week off schedule. In contrast with murine studies, patupilone has a relatively prolonged terminal half-life in humans. The partial responses in patients previously treated with taxanes is consistent with promising preclinical results.

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