The Clinical Pharmacokinetics of Quinapril

Angiology ◽  
1989 ◽  
Vol 40 (4_part_2) ◽  
pp. 351-359 ◽  
Author(s):  
Stephen C. Olson ◽  
Ann Marie Horvath ◽  
Barbara M. Michniewicz ◽  
Allen J. Sedman ◽  
Wayne A. Colburn ◽  
...  
Keyword(s):  
Half Life ◽  
Peak Plasma ◽  
Dose Range ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Clinical Pharmacokinetics ◽  
Q 61 ◽  
Dose Proportional

Quinapril (Q) and quinaprilat (QT) pharmacokinetics are dose pro portional following single oral 2.5- to 80-mg Q doses. Q absorption and hy drolysis to QT is rapid with peak Q and QT concentrations occurring one and two hours postdose, respectively. Peak plasma QT concentrations were approximately fourfold higher than those of Q (923 vs 207 ng/mL follow ing 40-mg Q). Dose-proportional QT area under the curve and dose-inde pendent percent of dose excreted in urine as QT demonstrate that the ex tent of Q conversion to QT is con stant over the dose range studied. Q and QT were eliminated from plasma with apparent half-lives of 0.8 and 1.9 hours and apparent plasma clear ances of 1,850 and 220 mL/min, re spectively, over the 2.5- to 80-mg dose range. Following oral 14C-Q, 61% and 37% of radiolabel was recovered in urine and feces, respectively. Q plus QT accounted for 46% of radioactiv ity circulating in plasma and 56% of that excreted in urine. Metabolism to compounds other than QT is not extensive. Two diketo piperazine metabolites of Q have been identified in plasma and urine, with approximately 6% of an admin istered dose excreted in urine as each of these metabolites. Peak plasma concentrations of these metabolites are similar to that of Q, and each is eliminated rapidly with a half-life of approximately one hour. Urinary ex cretion profiles indicate the presence of other minor metabolites. In summary, the absorption of Q and conversion to QT is rapid and dose-proportional, subsequent clear ance of both Q and QT is independ ent of dose, and metabolism to compounds other than QT is not ex tensive.

Oblimersen (OBL; Genasense®), a Phosphorothioate (PS) Bcl-2 Antisense Oliogonucleotide (ASO), Can Be Safely Administered by Bolus Subcutaneous (SC) Injection and Brief IV Infusion.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4724-4724
Author(s):  
Anthony Tolcher ◽  
Thomas Julian ◽  
Anila Qureshi
Keyword(s):  
Dose Level ◽  
Dose Escalation ◽  
Complement Activation ◽  
Peak Plasma ◽  
Performance Status ◽  
Dose Range ◽  
Plasma Concentrations ◽  
Lymphocytic Leukemia ◽  
Cytotoxic Drugs ◽  
Dose Proportional

Abstract Background: Oblimersen (OBL) is an 18-mer PS-ASO that down-regulates Bcl-2 and amplifies the activity of cytotoxic drugs in patients (pts) with chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), and melanoma. PS-ASOs like OBL are commonly administered by continuous intravenous infusion (CIV) in order to avoid high peak plasma concentrations that have been associated with cardiovascular collapse, complement activation, and death in primates. However, we consistently observed no such reactions in patients who received inadvertent overdoses of OBL. Furthermore, preclinical studies in xenograft tumors in mice indicated that intratumoral uptake and retention of OBL was enhanced with short IV infusion. Given the inconvenience of CIV and based on recent preclinical data, we evaluated the safety and pharmacokinetics (PK) of OBL administered as weekly subcutaneous (SC) injection, a brief 2-hr IV infusion for 5 days, and a weekly 2-hr infusion. Methods: Eligible pts had: advanced solid tumors; no available standard therapy; adequate organ function; and ECOG performance status of 0 to 2. In the SC study, single doses of 75, 150, and 225 mg were given to 8 pts, followed by a multiple dose study at 150 mg, 225 mg, and 300 mg. Pts received OBL by 2-hr IV infusion once weekly for 3 weeks (Days 1, 8, 15) starting at a dose of 300 mg and increasing in increments of 100 mg to the maximum tolerated dose (MTD). Blood samples were obtained for complement, Bcl-2, and PK analyses. Dose escalation utilized an accelerated dose escalation schedule. Results: Single pt cohorts were treated at each 2-hr dose level ranging from 300 to 800 mg. Syncope occurred in 1 pt treated with 900 mg, but treatment of 2 additional pts at this dose was uneventful. At the 1000 mg dose level, all pts experienced fever, chills, and moderate decreases in blood pressure, generally limited to the first infusion, which were not felt to be dose-limiting. The PK were dose-proportional over the 300 to 900 mg dose range. AUC and Cmax levels nearly were dose-proportional, and dose-normalized AUC and Cmax values were constant. Cmax values at 900 mg were > 50 μg/mL, and exceeded by >10-fold the Css of CIV schedules in solid tumor pts. There was no change in metabolism or plasma clearance with increasing doses. Large inter-patient variability was observed; however, intra-patient variability was low, as indicated by a coefficient of variation of < 20% for Cmax values obtained on Days 1, 8, and 15. No consistent pattern in complement activation was observed. One patient with metastatic NSCLC remains on study at 14 weeks with a 10% reduction in tumor size. OBL given by SC injection was associated with a Grade 1 erythematous rash at the injection site in all pts, which resolved within 7 days. AUC0–24 exposure at the 225-mg SC dose was similar to previously established 24-h steady-state AUCs after 3 mg/kg by CIV infusion. Conclusions: OBL AUC exposure from a single SC injection is similar to that observed using the 3mg/kg daily dose level administered by CIV to pts with CLL. OBL can also be administered safely by 2-hr IV infusion at weekly doses up to 1,000 mg. Corticosteroids are being tested to evaluate whether constitutional reactions can be ameliorated, and then a twice-per-week schedule will be designed to examine OBL-induced down-regulation of Bcl-2 alone and in combination with cytotoxic drugs in specific diseases.

scholarly journals Intravenous and Intraperitoneal Pharmacokinetics of Dalbavancin in Peritoneal Dialysis Patients

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
E. T. Van Matre ◽  
I. Teitelbaum ◽  
T. H. Kiser
Keyword(s):  
Peritoneal Dialysis ◽  
Half Life ◽  
Peritoneal Fluid ◽  
Area Under The Curve ◽  
Terminal Phase ◽  
Dialysis Patients ◽  
Time Data ◽  
Open Label ◽  
Gram Positive ◽  
Clinical Pharmacokinetics

ABSTRACT Dalbavancin offers a possible treatment option for infectious peritonitis associated with peritoneal dialysis (PD) due to its coverage of Gram-positive bacteria and pharmacokinetic properties. We aimed to evaluate the clinical pharmacokinetics (PK) and pharmacodynamics of dalbavancin in a prospective, randomized, open-label, crossover PK study of adult patients with end-stage renal disease ESRD who were receiving PD. Sampling occurred prior to a single 30-min infusion of dalbavancin at 1,500 mg and at 1, 2, 3, 4, and 6 h and 7 and 14 days postadministration. Concentration-time data were analyzed via noncompartmental analysis. Pharmacodynamic parameters against common infectious peritonitis-causing pathogens were evaluated. Ten patients were enrolled. Patients were a median of 55 years old and had a median weight of 78.2 kg, 50% were female, and 70% were Caucasian. The terminal plasma half-life of dalbavancin was 181.4 ± 35.5 h. The day 0 to day 14 dalbavancin mean area under the curve (AUC) was 40,573.2 ± 9,800.3 mg·h/liter. The terminal-phase half-life of dalbavancin within the peritoneal fluid was 4.309 × 108 ± 1.140 × 109 h. The day 0 to day 14 dalbavancin mean peritoneal fluid AUC was 2,125.0 ± 1,794.3 mg·h/liter. The target plasma AUC/MIC was attained with the intravenous dose in all 10 patients for all Staphylococcus and Streptococcus species at the recommended MIC breakpoints. The intraperitoneal arm of the study was stopped early, because the first 3 patients experienced moderate to severe pain and bloating within 1 h following the administration of dalbavancin. Dalbavancin at 1,500 mg administered intravenously can be utilized without dose adjustment in peritoneal dialysis patients and will likely achieve the necessary peritoneal fluid concentrations to treat peritonitis caused by typical Gram-positive pathogens.

Phase I and Pharmacokinetic Study of Farnesyl Protein Transferase Inhibitor R115777 in Advanced Cancer

2000 ◽  
Vol 18 (4) ◽  
pp. 927-927 ◽  
Author(s):  
J. Zujewski ◽  
I.D. Horak ◽  
C.J. Bol ◽  
R. Woestenborghs ◽  
C. Bowden ◽  
...  
Keyword(s):  
Peak Plasma ◽  
Performance Status ◽  
Dose Range ◽  
Plasma Concentrations ◽  
Oral Drug ◽  
Total Daily Dose ◽  
Pharmacokinetic Data ◽  
Metastatic Colon Cancer ◽  
Phase Ii Trials ◽  
Farnesyl Protein Transferase

PURPOSE: To determine the maximum-tolerated dose, toxicities, and pharmacokinetic profile of the farnesyl protein transferase inhibitor R115777 when administered orally bid for 5 days every 2 weeks. PATIENTS AND METHODS: Twenty-seven patients with a median age of 58 years received 85 cycles of R115777 using an intrapatient and interpatient dose escalation schema. Drug was administered orally at escalating doses as a solution (25 to 850 mg bid) or as pellet capsules (500 to 1300 mg bid). Pharmacokinetics were assessed after the first dose and the last dose administered during cycle 1. RESULTS: Dose-limiting toxicity of grade 3 neuropathy was observed in one patient and grade 2 fatigue (decrease in two performance status levels) was seen in four of six patients treated with 1,300 mg bid. The most frequent clinical grade 2 or 3 adverse events in any cycle included nausea, vomiting, headache, fatigue, anemia, and hypotension. Myelosuppression was mild and infrequent. Peak plasma concentrations of R115777 were achieved within 0.5 to 4 hours after oral drug administration. The elimination of R115777 from plasma was biphasic, with sequential half-lives of about 5 hours and 16 hours. There was little drug accumulation after bid dosing, and steady-state concentrations were achieved within 2 to 3 days. The pharmacokinetics were dose proportional in the 25 to 325 mg/dose range for the oral solution. Urinary excretion of unchanged R115777 was less than 0.1% of the oral dose. One patient with metastatic colon cancer treated at the 500-mg bid dose had a 46% decrease in carcinoembryonic antigen levels, improvement in cough, and radiographically stable disease for 5 months. CONCLUSION: R115777 is bioavailable after oral administration and has an acceptable toxicity profile. Based upon pharmacokinetic data, the recommended dose for phase II trials is 500 mg orally bid (total daily dose, 1,000 mg) for 5 consecutive days followed by 9 days of rest. Studies of continuous dosing and studies of R115777 in combination with chemotherapy are ongoing.

Pharmacokinetics of L-arginine during chronic administration to patients with hypercholesterolaemia

1999 ◽  
Vol 96 (2) ◽  
pp. 199-207 ◽  
Author(s):  
Oranee TANGPHAO ◽  
Stephan CHALON ◽  
Heitor MORENO ◽  
Brian B. HOFFMAN ◽  
Terrence F. BLASCHKE
Keyword(s):  
Nitric Oxide ◽  
Animal Studies ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Chronic Administration ◽  
Pharmacokinetic Studies ◽  
Acute Administration ◽  
Term Administration ◽  
Endothelial Nitric Oxide

Acute administration of L-arginine, the precursor of endothelial nitric oxide, has been shown to improve endothelial function in hypercholesterolaemic rabbits and humans. Animal studies suggest that this beneficial effect, which is thought to be related to the increased availability of nitric oxide, may not be sustained during chronic oral administration. Pharmacokinetic alterations may contribute to this observation. The present study was designed to examine the disposition of L-arginine in hypercholesterolaemic subjects during long-term administration. Plasma L-arginine concentrations were determined by HPLC in 10 patients (eight women and two men; mean age 46±16 years) after an intravenous dose of 10 or 30 g and an oral dose of 5 or 7 g. Pharmacokinetic studies were performed at regular intervals (4 weeks) during a 12-week period of oral L-arginine administration (14–21 g/day). The average plasma L-arginine concentrations before (baseline) and during administration were 16.1±1.2 and 22.5±1.3 μg/ml respectively (P< 0.05). Plasma concentrations of L-arginine remained above baseline throughout weeks 2–12. The L-arginine exposure, expressed as a normalized area-under-the-curve for 8 h (AUC0–8) after oral or intravenous doses during the first visit, was 894.4±118.7 and 1837.8±157.0 units respectively. There were no significant changes in peak plasma L-arginine concentrations or in the AUC0–8 after oral and intravenous doses during subsequent visits (P> 0.05). The mean non-renal clearance of L-arginine during the four visits remained constant. Knowledge of the pharmacokinetics of L-arginine may be useful in the design of clinical trials involving this agent, as well as in the interpretation of the pharmacodynamics of this important precursor of nitric oxide.

Clinical pharmacokinetics (PK) of BMS-936558, a fully human anti-PD-1 monoclonal antibody.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS2622-TPS2622 ◽  
Author(s):  
Shruti Agrawal ◽  
Yan Feng ◽  
Georgia Kollia ◽  
Sally Saeger ◽  
Martin Ullmann ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Body Weight ◽  
Half Life ◽  
Dose Range ◽  
Volume Of Distribution ◽  
Wide Range ◽  
Body Weights ◽  
Clinically Significant ◽  
Potentially Clinically Significant ◽  
Dose Proportional

TPS2622 Background: BMS-936558 is a fully human IgG4 monoclonal antibody targeted against human Programed Death-1 (PD1) receptor on activated T and B lymphocytes. Blocking of PD-1 prevents these activated cells from becoming anergic, thereby maintaining anti-tumor immunologic activity. Methods: The PK of BMS-936558 was characterized with data from a single ascending dose (SAD) and a multiple ascending dose (MAD) study in subjects with advanced solid malignancies. Subjects received a single IV infusion of 0.3 to 10 mg/kg BMS-936558 in the SAD study (MDX-1106-01 Study) and 0.1 to 10 mg/kg BMS-936558 every two weeks in the MAD study (MDX-1106-03/CA209003 Study). The PK of BMS-936558 was characterized by non-compartmental analysis of intensively sampled PK data from a SAD study, as well as by population PK analysis of available intensive and sparse PK data from the SAD and MAD studies, respectively. Results: The PK of BMS-936558 is linear in the studied dose range with dose-proportional increase in Cmax and AUC with low to moderate (20-44%) inter-subject variability. Geometric mean clearance ranged from 0.13 - 0.19 mL/h/kg, whereas mean volume of distribution ranged from 83 -113 mL/kg. The range of mean terminal elimination half-life of BMS-936558 is 17 to 25 days which is consistent with half-life of endogenous IgG4. BMS-936558 PK was adequately described by a linear two-compartment model, and there was no evidence of a contribution of target mediated drug disposition to drug elimination within tested dose range. Body weight and gender are potentially clinically significant covariate for both clearance and volume of distribution (> 20% effect); and baseline CRP, LDH, and albumin are potentially clinically significant covariates for CL. The body weight normalized dosing employed produces trough concentrations that are approximately constant over a wide range of body weights. Conclusions: The pharmacokinetics of BMS-936558 is dose-proportional and body weight normalized dosing is appropriate to ensure consistent exposure over a wide range of body weights.

Results of a phase I trial of the proteasome inhibitor carfilzomib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7077-7077
Author(s):  
Jennifer Ann Woyach ◽  
Joseph M. Flynn ◽  
Jeffrey Alan Jones ◽  
Leslie A. Andritsos ◽  
Margaret Lucas ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Level ◽  
Phase I Trial ◽  
Dose Range ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Lymphocytic Leukemia ◽  
Maximum Plasma ◽  
Maximal Dose

7077 Background: CLL is an incurable malignancy, and survival for patients (pts) with relapsed disease is limited. Carfilzomib (CFZ) has shown efficacy in multiple myeloma, and our group has shown significant in vitro activity in primary CLL cells. Therefore, we have undertaken a phase I trial of this agent in CLL. Methods: This is a single institution phase I trial of CFZ in pts with relapsed or refractory CLL. Primary endpoints were to determine maximal tolerated dose (MTD) and describe toxicity. Pts with CLL relapsed after at least one therapy were enrolled using a 3x3 design. CFZ was administered on the standard myeloma schedule. The first two doses were administered at 20 mg/m2 with remainder given at doses starting at 27 mg/m2 for dose level 1 with escalation to 56 mg/m2. Results: 17 pts received at least 1 dose of CFZ. 12 pts completed at least 1 cycle of therapy, with the remaining 5 experiencing PD during cycle 1. The MTD was not reached, with 3 pts accrued to each dose level to the maximal dose tested without dose limiting toxicity. Most adverse events (AE) were grade (G) 1 or 2. G3/4 AE were quickly reversible and included G3 neutropenia (4 pts), G4 neutropenia (2), G3 febrile neutropenia (1), and G3 thrombocytopenia (3). G1/2 toxicities observed in ≥ 20% of pts included anemia (10), thrombocytopenia (7), and hypocalcemia (8). Median number of cycles was 3, with 9 pts achieving stable disease after 2 cycles. Of 3 pts enrolled at maximal dose level, 2 remain on therapy after 5 and 7 months, with 1 achieving a clinical partial response. Of 5 evaluable pts, at least 50% proteasome inhibition was seen in all at 1 hour, with minimal recovery at 24 hours. PK was best characterized by a two-compartment model. Maximum plasma concentrations across all dose levels ranged from 0.81 to 8.1 uM. Across the evaluated dose range, area under the curve increased in an apparent dose-proportional manner. Conclusions: Despite relatively limited efficacy in this study, CFZ has acceptable toxicity in CLL, with no MTD identified up to 56 mg/m2. This suggests that CFZ may be better studied in CLL using a different schedule or in combination with other active agents. Clinical trial information: NCT01212380.

scholarly journals Kisspeptin receptor agonist (FTM080) increased plasma concentrations of luteinizing hormone in anestrous ewes

2015 ◽  
Author(s):  
Brian K Whitlock ◽  
Joseph A Daniel ◽  
Lisa L Amelse ◽  
Valeria M Tanco ◽  
Kelly A Chameroy ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Half Life ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Similar Efficacy ◽  
Comparable Efficacy ◽  
Breeding Management ◽  
Gonadotropic Axis

Kisspeptin receptor (KISS1R) agonists with increased half-life and similar efficacy to kisspeptin in vitro may provide beneficial applications in breeding management of many species. However, many of these agonists have not been tested in vivo. These studies were designed to test and compare the effects of a KISS1R agonist (FTM080) and kisspeptin on luteinizing hormone (LH) in vivo. In experiment 1 (pilot study), sheep were treated with FTM080 (500 pmol/kg BW) or sterile water (VEH) intravenosuly. Blood was collected every 15 min before (1 hr) and after (1 hr) treatment. In experiment 2, sheep were treated with KP-10 (human Metastin 45-54; 500 pmol/kg BW), one of three dosages of FTM080 [500 (FTM080:500), 2500 (FTM080:2500), or 5000 (FTM080:5000) pmol/kg BW], or VEH intravenously. Blood was collected every 15 min before (1 hr) and after (4 hr) treatment. In experiment 1, FTM080:500 increased (P < 0.05) plasma LH concentrations when compared to VEH. The area under the curve (AUC) of LH following FTM080:500 treatment was also increased (P < 0.05). In experiment 2, plasma LH concentrations increased (P < 0.05) following treatment with KP-10 and FTM080:5000 when compared to VEH and FTM080:500. The AUC of LH following KP-10 was greater than (P < 0.05) all other treatments and the AUC of LH following FTM080:5000 was greater than (P < 0.05) all treatments except KP-10. These data provide evidence to suggest that FTM080 stimulates the gonadotropic axis of ruminants in vivo. Any increased half-life and comparable efficacy of FTM080 to KP-10 in vitro does not appear to translate to in vivo in sheep.

scholarly journals Kisspeptin receptor agonist (FTM080) increased plasma concentrations of luteinizing hormone in anestrous ewes

PeerJ ◽  
2015 ◽  
Vol 3 ◽  
pp. e1382 ◽  
Author(s):  
Brian K. Whitlock ◽  
Joseph A. Daniel ◽  
Lisa L. Amelse ◽  
Valeria M. Tanco ◽  
Kelly A. Chameroy ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Half Life ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Similar Efficacy ◽  
Comparable Efficacy ◽  
Breeding Management ◽  
Gonadotropic Axis

Kisspeptin receptor (KISS1R) agonists with increased half-life and similar efficacy to kisspeptinin vitromay provide beneficial applications in breeding management of many species. However, many of these agonists have not been testedin vivo. These studies were designed to test and compare the effects of a KISS1R agonist (FTM080) and kisspeptin on luteinizing hormone (LH)in vivo. In experiment 1 (pilot study), sheep were treated with FTM080 (500 pmol/kg BW) or sterile water (VEH) intravenosuly. Blood was collected every 15 min before (1 h) and after (1 h) treatment. In experiment 2, sheep were treated with KP-10 (human Metastin 45-54; 500 pmol/kg BW), one of three dosages of FTM080 (500 (FTM080:500), 2500 (FTM080:2500), or 5000 (FTM080:5000) pmol/kg BW), or VEH intravenously. Blood was collected every 15 min before (1 h) and after (4 h) treatment. In experiment 1, FTM080:500 increased (P< 0.05) plasma LH concentrations when compared to VEH. The area under the curve (AUC) of LH following FTM080:500 treatment was also increased (P< 0.05). In experiment 2, plasma LH concentrations increased (P< 0.05) following treatment with KP-10 and FTM080:5000 when compared to VEH and FTM080:500. The AUC of LH following KP-10 was greater than (P< 0.05) all other treatments and the AUC of LH following FTM080:5000 was greater than (P< 0.05) all treatments except KP-10. These data provide evidence to suggest that FTM080 stimulates the gonadotropic axis of ruminantsin vivo. Any increased half-life and comparable efficacy of FTM080 to KP-10in vitrodoes not appear to translate toin vivoin sheep.

Pharmacokinetics and investigation of optimal dose ertapenem in intermittent hemodialysis patients

2018 ◽  
Vol 34 (10) ◽  
pp. 1766-1772 ◽  
Author(s):  
Lama M Hsaiky ◽  
Francine D Salinitri ◽  
Judy Wong ◽  
Sin-Ling T Jennings ◽  
Neha H Desai ◽  
...  
Keyword(s):  
Half Life ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Optimal Dose ◽  
Hemodialysis Patients ◽  
Pharmacokinetic Parameters ◽  
Intermittent Hemodialysis ◽  
Pharmacokinetic Studies ◽  
Open Label ◽  
Serious Adverse Events

Abstract Background Previous pharmacokinetic studies demonstrated an increase in serum ertapenem concentrations with decreasing kidney function, including patients receiving renal replacement therapy. This study evaluated the pharmacokinetic parameters of ertapenem in patients receiving hemodialysis. Methods This prospective, single-center, open-label study examined the pharmacokinetics of a single intravenous (IV) dose of ertapenem 1 g in seven hospitalized noninfected patients undergoing hemodialysis. Blood samples were collected prior to ertapenem administration and at 0.5, 1, 2, 6, 12 and 48 hours (h) after administration. Ertapenem concentrations were determined by validated liquid chromatography mass spectrometry assay. Results Following an IV bolus of 1 g ertapenem, plasma concentrations declined relatively slowly with a mean ±standard deviation (SD) elimination half-life of 19.3 ±6.6 h. Plasma concentrations were similar in all subjects, with maximum mean plasma concentration observed of 343±48 µg/mL postdose. The mean ±SD values for systemic plasma clearance (CL) and volume of distribution at steady state (Vss) were 2±0.5 mL/min and 3295±1187 mL, respectively. The area under the curve for 0 h–∞ (AUCinf) was 7494 ±1424 h•µg/mL. No gender effect was observed and no serious adverse events were reported. Conclusions Ertapenem half-life was prolonged in hemodialysis patients. Considering the nonrenal clearance and the expected 70% removal with high-efficacy hemodialysis, the dose of 1 g ertapenem, three times weekly, after hemodialysis may produce pharmacodynamically sufficient exposure for potential antimicrobial efficacy. Further studies are warranted to assess the clinical efficacy and safety of this dose with prolonged duration of therapy.

scholarly journals Pharmacokinetics of Tinidazole in Chinese subjects: Comparison of Mongolian, Korean, Hui, Uighur and Han nationalities

2009 ◽  
Vol 12 (2) ◽  
pp. 175 ◽  
Author(s):  
Xin-Yu Chang ◽  
Tao Guo ◽  
Dong-Ya Xia
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Half Life ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Elimination Rate ◽  
Area Under The Curve ◽  
Elimination Half ◽  
Pharmacokinetic Properties ◽  
Chinese Subjects

ABSTRACT - Purpose. This study investigated the pharmacokinetics of tinidazole in subjects of five different Chinese nationalities (Han, Mongolian, Korean, Hui, and Uighur). Methods. Fifty healthy subjects (five male and five female of each nationality) were recruited for the study, and each received 1 g tinidazole. A total of 14 blood samples were collected over a 72-hour period after administration. Results. Pharmacokinetic profiles, including area under the curve from time zero to infinity (AUC0-inf), peak plasma concentration (Cmax), time to reach Cmax (tmax), oral clearance (CL/F), elimination rate constant (Ke), and elimination half-life (t1/2), were determined following a single oral dose of tinidazole. The respective pharmacokinetic properties of Han, Mongolian, Korean, Hui, and Uighur nationalities were: half-life (h): 16.94±2.40, 16.40±1.79, 16.63±1.82, 16.81±1.56, 14.34±1.92; Cmax (μg/mL): 19.04±2.42, 19.22±4.93, 20.83±3.33, 20.25±4.05, 18.81±3.10; AUC0-inf (h•μg/mL): 483.13±65.65, 479.70±99.74, 511.07±53.47, 514.25±130.78, 388.58±37.37. The t1/2 and AUC0-inf of Uighur subjects were significantly lower (p =0.023, 0.011) and the CL/F and Ke were significantly higher (p = 0.003, 0.013) than those of other nationalities. After normalization by weight, the differences in AUC0-inf and CL/F between Uigur subjects and those of other races were still significant. Conclusions. The results indicate that ethnicity had significant impact on the pharmacokinetics of tinidazole after a single oral dose in healthy volunteers of different nationalities in China.

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