An initial dosing method for teicoplanin based on the area under the serum concentration time curve required for MRSA eradication

2011 ◽  
Vol 17 (2) ◽  
pp. 297-300 ◽  
Author(s):  
Naoko Kanazawa ◽  
Kazuaki Matsumoto ◽  
Tomohide Fukamizu ◽  
Akari Shigemi ◽  
Keiko Yaji ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Time Curve ◽  
Concentration Time ◽  
Dosing Method

scholarly journals PHARMACODYNAMICS EFFECT OF METHYLPREDNISOLONE TABLETS ON THE SERUM CONCENTRATION OF ANNEXIN A1: IN VIVO COMPARATIVE STUDY BETWEEN GENERIC AND INNOVATOR DRUG

2019 ◽  
Vol 12 (1) ◽  
pp. 414
Author(s):  
Hansen Nasif ◽  
Henny Lucida ◽  
Yanwirasti Yanwirasti ◽  
Yufri Aldi ◽  
Yori Yuliandra
Keyword(s):  
Serum Concentration ◽  
Peak Concentration ◽  
Peak Time ◽  
Annexin A1 ◽  
Onset Of Action ◽  
Time Curve ◽  
Concentration Time ◽  
Significant Difference ◽  
Generic Products

Objective: The aims of this study were to investigate the comparative pharmacodynamics effect of methylprednisolone (MP) innovator, MP branded generic, and MP generic products to the serum concentration of annexin A1 (AnxA1).Methods: It was conducted by two-way crossover design in male rabbits. AnxA1 was measured at 0, 0.5, 1, 2, 3, 5, 7, and 9 h after the administration of the drugs. The peak concentration (Cmax), the time at which the peak concentration was achieved (Tmax), and the area under the plasma concentration-time curve (AUC) were also determined.Results: The highest concentration and widest AUC of AnxA1 were obtained in MP innovator drug. MP innovator and branded generic reaches the peak time (Tmax) at the third 3rd h, while the MP generic reaches the peak time at the 5th h. The results showed that there was no significant difference in the serum concentration of AnxA1 between MP tablets after analyzed with a one-way analysis of variance.Conclusion: It could be concluded that the innovator drug of MP tablet gave the same effect on the serum concentration of AnxA1 than its generic counterparts, but an onset of action MP innovator and branded generic is faster than the generic product.

Optimizing Vancomycin Dosing through Pharmacodynamic Assessment Targeting Area under the Concentration-Time Curve/Minimum Inhibitory Concentration

2009 ◽  
Vol 44 (9) ◽  
pp. 751-765 ◽  
Author(s):  
C. Andrew Deryke ◽  
Donald P. Alexander
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Serum Concentration ◽  
Clinical Outcomes ◽  
Inhibitory Concentration ◽  
Health Care Systems ◽  
Time Curve ◽  
Concentration Time ◽  
Trough Serum Concentration ◽  
Trough Serum

Because of its activity against multidrug resistant gram-positive organisms, vancomycin is one of the antimicrobials most utilized in health care systems worldwide. Despite its widespread use, application of the pharmacodynamic principles governing vancomycin efficacy are not frequently considered in contemporary clinical practice. Although the vancomycin trough serum concentration has been used historically to assess the adequacy of a prescribed dose, data validating that this practice leads to improved patient outcomes do not exist. Alternatively, both in vitro and clinical outcomes data demonstrate improved results when an area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) of 400 mcg•h/mL or greater is achieved. This article describes the process through which individualized vancomycin dosing regimens targeting an AUC/MIC of 400 mcg•h/mL or greater, rather than trough serum concentration, at the beside can be derived. The equations, methodology, thought processes, benefits, potential pitfalls, and practical applicability of this method are specifically examined. Obtaining the actual MIC value—not an interpretation—from the microbiology laboratory and/or the MIC distribution for Staphylococcus aureus within one's own institution is essential for implementation of this method. Although vancomycin dosing recommendations suggested in contemporary practice guidelines are likely adequate for most patients, using the methods described here may lead to improved clinical outcomes for nonstandard conditions in patients who are critically ill and would benefit from an individualized dosing approach.

scholarly journals Carboplatin and Etoposide With or Without Palifosfamide in Untreated Extensive-Stage Small-Cell Lung Cancer: A Multicenter, Adaptive, Randomized Phase III Study (MATISSE)

2017 ◽  
Vol 35 (23) ◽  
pp. 2619-2623 ◽  
Author(s):  
Shadia I. Jalal ◽  
Philip Lavin ◽  
Gregory Lo ◽  
Francois Lebel ◽  
Lawrence Einhorn
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Serum Concentration ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Time Curve ◽  
Concentration Time ◽  
Phase Iii Study ◽  
Extensive Stage

Purpose To evaluate the efficacy of the addition of palifosfamide to carboplatin and etoposide in extensive stage (ES) small-cell lung cancer (SCLC). Patients and Methods MATISSE was a randomized, open-label, adaptive phase III study. Previously untreated patients with ES SCLC were randomly assigned in a 1:1 fashion to receive carboplatin at area under the serum concentration-time curve 5 on day 1 plus etoposide 100 mg/m2 per day on days 1 to 3 every 21 days (CE) or carboplatin at area under the serum concentration-time curve 4 on day 1 plus etoposide 100 mg/m2 per day plus palifosfamide 130 mg/m2 per day on days 1 to 3 every 21 days (PaCE). The primary end point was overall survival. Results In all, 188 patients were enrolled; 94 patients received CE and 94 patients received PaCE. The median age on both arms was 61 years. Six cycles of chemotherapy were completed on both arms of the study by approximately 50% of the patients. Serious adverse events were documented and did not differ significantly between patients receiving PaCE and those receiving CE. Median overall survival was similar between both arms with 10.03 months on PaCE and 10.37 months on CE ( P = .096). Conclusion The addition of palifosfamide to CE failed to improve survival in ES SCLC.

Safety, Pharmacokinetic, and Pharmacodynamic Phase I Dose-Escalation Trial of PF-00562271, an Inhibitor of Focal Adhesion Kinase, in Advanced Solid Tumors

2012 ◽  
Vol 30 (13) ◽  
pp. 1527-1533 ◽  
Author(s):  
Jeffrey R. Infante ◽  
D. Ross Camidge ◽  
Linda R. Mileshkin ◽  
Eric X. Chen ◽  
Rodney J. Hicks ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Dose Escalation ◽  
Group Performance ◽  
Geometric Mean ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Time Curve ◽  
Concentration Time

Purpose PF-00562271 is a novel inhibitor of focal adhesion kinase (FAK). The objectives of this study were to identify the recommended phase II dose (RP2D) and assess safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of PF-00562271. Patients and Methods Part 1 was a dose escalation without and with food. Part 2 enrolled specific tumor types in an expansion at the RP2D and also assessed the effect of PF-00562271 on single-dose midazolam PK in a subgroup of patients. Results Ninety-nine patients (median age, 60 years; 98% with Eastern Cooperative Oncology Group performance status of 0 or 1) were treated in 12 fasting and three fed cohorts. The 125-mg twice-per-day fed dose was deemed the maximum-tolerated dose (MTD) and RP2D. Grade 3 dose-limiting toxicities included headache, nausea/vomiting, dehydration, and edema. Nausea was the most frequently observed toxicity (60% of patients, all grades 1 or 2 at RP2D). PF-00562271 exposure increased with increasing dose; serum concentration–time profiles showed characteristic nonlinear disposition. Steady-state exposures were reached within 1 week. On coadministration, geometric mean values of midazolam maximal observed serum concentration and area under the serum concentration–time curve increased by 60% and more than two-fold, respectively. Of 14 patients evaluable by [18F]fluorodeoxyglucose positron emission tomography in the expansion cohorts, seven metabolic responses were observed. With conventional imaging, 31 patients had stable disease at first restaging scans, and 15 of these remained stable for six or more cycles. Conclusion The MTD and RP2D of PF-00562271 is 125 mg twice per day with food. PF-00562271 displayed time- and dose-dependent nonlinear PK and is likely a potent CYP 3A inhibitor. This first-in-class study supports further investigation of FAK as a promising therapeutic target.

scholarly journals Successful Treatment of Invasive MRSA Infections in Children Using Area Under the Vancomycin Concentration-Time Curve Divided by the Minimum Inhibitory Concentration (AUC/MIC) to Measure Vancomycin Exposure

2021 ◽  
Vol 1 (S1) ◽  
pp. s31-s31
Author(s):  
Leslie Chiang ◽  
Alice Pong ◽  
John Bradley ◽  
Paige Anderson ◽  
William Murray
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Clinical Outcomes ◽  
Inhibitory Concentration ◽  
Renal Toxicity ◽  
Time Curve ◽  
Vancomycin Concentration ◽  
Concentration Time ◽  
Serum Trough ◽  
Trough Concentrations ◽  
Dosing Method

Background: Vancomycin is the treatment of choice for invasive methicillin-resistant Staphylococcus aureus (MRSA) infections. Previous guidelines issued by the Infectious Diseases Society of America (IDSA) recommended targeting vancomycin serum trough concentrations of 15–20 mg/L; however, troughs <15 mg/L are also associated with increased odds of renal toxicity. To minimize toxicity, recently updated ASHP/IDSA/PIDS vancomycin dosing guidelines recommend the use of an area under the vancomycin concentration-time curve divided by the minimum inhibitory concentration (AUC/MIC) pharmacodynamic index to measure vancomycin exposure, with an AUC/MIC ratio >400 correlating with clinical efficacy. However, data on vancomycin therapeutic drug monitoring (TDM) in children are limited. Our institutional practice since January 2009 has been to use AUC/MIC, rather than serum trough concentrations, to guide vancomycin dosing. In this study, we describe clinical outcomes in vancomycin-treated children with invasive MRSA infections using this dosing method. Methods: We performed a retrospective chart review of children hospitalized with invasive MRSA infections between 2006 and 2019 at Rady Children’s Hospital in San Diego, California. Clinical, microbiologic, and pharmacologic data including the site of MRSA infection, clinical failure or cure, occurrence of acute kidney injury (AKI), vancomycin MIC, vancomycin AUC, and serum trough concentrations were collected. Results: In total, 61 invasive MRSA cases were reviewed: 20 were admitted January 2016 through December 2008, and 41 were admitted January 2009 through June 2019 (Figure 1). Most patients did not have medical comorbidities. The most common types of infections were primary bacteremia (34%) and osteomyelitis (32%). Of 61 children, 50 (82%) had positive clinical outcomes regardless of vancomycin dosing method. Of 20 patients, 8 (40%) admitted prior to January 2009 developed AKI, compared with 5 (12%) of 41 patients admitted after January 2009. Conclusions: In our retrospective review, most patients had clinically successful outcomes regardless of which dosing strategy was used. We found higher rates of renal toxicity in patients who were admitted prior to 2009, with TDM based on measuring peak and trough concentrations, compared with those using AUC/MIC for TDM. Our findings suggest that AUC/MIC TDM for invasive MRSA infections may be associated with lower rates of renal toxicity.Funding: NoDisclosures: None

scholarly journals Comparison of two biosimilarity studies of FKB327 with the adalimumab reference product: randomized phase 1 studies of single-blind, single-dose subcutaneous injection in healthy Japanese male participants

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Takuma Yonemura ◽  
Rie Yazawa ◽  
Miwa Haranaka ◽  
Kazuki Kawakami ◽  
Masayuki Takanuma ◽  
...  
Keyword(s):  
Single Dose ◽  
Serum Concentration ◽  
Subcutaneous Injection ◽  
Reference Product ◽  
Time Curve ◽  
Treatment Groups ◽  
Concentration Time ◽  
Japanese Male ◽  
To Receive ◽  
Single Blind

Abstract Background FKB327 has been developed as a biosimilar of the adalimumab reference product (RP). We compared the pharmacokinetics (PK), safety, and immunogenicity of FKB327 with those of the adalimumab RP after a single dose by subcutaneous (SC) injection in Japanese male participants. Methods Two randomized, single-blind, single-dose studies were conducted in healthy Japanese male participants to compare PK characteristics between FKB327 and the RP. Study 1 included 130 participants who were randomized in a 1:1 ratio to receive a subcutaneous injection of 40 mg of either FKB327 or the RP into the abdomen. In Study 2, another 130 subjects were randomized in a 1:1 ratio to receive either drug as in Study 1, but the drug administration site was changed to the thigh. The primary PK endpoints of both studies were area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t) and maximum serum concentration; area under the concentration-time curve from time zero to 360 h was also evaluated as one of the primary endpoints in Study 1. Biosimilarity in terms of pharmacokinetics was determined if the 90% confidence interval of the mean difference in geometric mean ratio of all primary PK parameters was within the prespecified equivalence criteria (0.80–1.25). Immunogenicity and safety were also evaluated as secondary endpoints. Results The serum concentration-time profiles were comparable between the FKB327 and the RP treatment groups in both studies. Primary PK parameters were within the prespecified bioequivalence range in Study 2, although AUC0-t was slightly outside the upper side of the range in Study 1. No differences in safety profile were observed in these studies. The incidence of anti-drug antibodies (ADAs) and impact of ADAs on PK profile were similar among the treatment groups in both studies. Conclusion Biosimilarity between FKB327 and the RP after a single 40-mg SC injection was confirmed in healthy Japanese male participants by modifying the study design. Trial registration jRCT2071200058 (https://jrct.niph.go.jp/en-latest-detail/jRCT2071200058, https://rctportal.niph.go.jp/en/detail?trial_id=jRCT2071200058) and jRCT2071200057 (https://jrct.niph.go.jp/en-latest-detail/jRCT2071200057, https://rctportal.niph.go.jp/en/detail?trial_id=jRCT2071200057). Retrospectively registered 25/11/2020.

scholarly journals Pharmacokinetics of a New Parenteral Oligosaccharide Antibiotic, SCH27899 (Ziracin), in Healthy Subjects

2001 ◽  
Vol 45 (3) ◽  
pp. 917-921 ◽  
Author(s):  
Osamu Kozawa ◽  
Toshihiko Uematsu ◽  
Hiroyuki Matsuno ◽  
Masayuki Niwa ◽  
Ken-Ichi Kohno ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Moderate Degree ◽  
Time Curve ◽  
Once Daily ◽  
Concentration Time ◽  
Japanese Male ◽  
Pharmacokinetic Properties ◽  
Repeated Doses ◽  
Total Body ◽  
Body Clearance

ABSTRACT The pharmacokinetic properties of an everninomicin antibiotic (SCH27899; Ziracin) were studied with healthy Japanese male volunteers by single (1, 3, 6, and 9 mg/kg of body weight) and multiple 60-min intravenous infusions (3, 6, and 9 mg/kg once daily for 10 consecutive days following a 2-day interval after the initial dose). At single doses the peak serum concentration and the area under the serum concentration-time curve linearly increased with the dose. While total body clearance (CL; 31.2 to 45.6 ml/kg/h) and percent cumulative urinary recovery as unchanged drug (4.9 to 7.1%) were rather constant irrespective of doses, the terminal half-life of γ phase (t 1/2γ; 14.2 to 19.6 h) were slightly prolonged at the higher two doses compared with the lower two doses. With repeated doses of SCH27899, a statistically significant decrease and increase were found in CL and t 1/2γ of about 36 and 21%, respectively, although these changes may be clinically irrelevant. The most commonly reported adverse events were local reactions such as erythema, pain, and palpable venous cord of mild to moderate degree around the injection site, which could be managed by changing the injection sites.

Effect of Food on Nifedipine Sustained-Release Preparation

DICP ◽  
1989 ◽  
Vol 23 (9) ◽  
pp. 662-665 ◽  
Author(s):  
Kazuyuki Ueno ◽  
Syuichi Kawashima ◽  
Kiyotaka Uemoto ◽  
Tomoko Ikada ◽  
Kazuyoshi Miyai ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Sustained Release ◽  
Time Curve ◽  
Maximum Serum ◽  
Sustained Release Preparation ◽  
Concentration Time ◽  
Release Preparation ◽  
Effect Of Food ◽  
Maximum Serum Concentration ◽  
The Mean

The effect of food on the bioavailability of a nifedipine sustained-release preparation was studied. Each of seven male volunteers received a single oral 20 mg dose with 100 mL of water under two conditions, fasting and after a meal, with a crossover after a seven-day wash-out period. Blood samples were drawn at time zero (just prior to dose), and 1, 2, 3, 4, 6, 8, 10, and 12 hours after dosing. Nifedipine assays were performed by gas chromatography. The area under the serum concentration-time curve (AUC) from 0 to 12 hours and maximum serum concentration (Cmax) were significantly increased by food. Blood pressure was significantly decreased by food. The mean AUC for fasting and meal conditions were 315.0 and 411.4 ng•h/mL, and the mean Cmax were 42.6 and 86.6 μg/mL, respectively. The results indicate that food may increase the bioavailability of nifedipine sustained-release preparation.

scholarly journals PHARMACODYNAMICS EFFECT OF METHYLPREDNISOLONE TABLETS ON THE SERUM CONCENTRATION OF ANNEXIN A1: IN VIVO COMPARATIVE STUDY BETWEEN GENERIC AND INNOVATOR DRUG

2019 ◽  
Vol 12 (1) ◽  
pp. 414
Author(s):  
Hansen Nasif ◽  
Henny Lucida ◽  
Yanwirasti Yanwirasti ◽  
Yufri Aldi ◽  
Yori Yuliandra
Keyword(s):  
Serum Concentration ◽  
Peak Concentration ◽  
Peak Time ◽  
Annexin A1 ◽  
Onset Of Action ◽  
Time Curve ◽  
Concentration Time ◽  
Significant Difference ◽  
Generic Products

Objective: The aims of this study were to investigate the comparative pharmacodynamics effect of methylprednisolone (MP) innovator, MP branded generic, and MP generic products to the serum concentration of annexin A1 (AnxA1).Methods: It was conducted by two-way crossover design in male rabbits. AnxA1 was measured at 0, 0.5, 1, 2, 3, 5, 7, and 9 h after the administration of the drugs. The peak concentration (Cmax), the time at which the peak concentration was achieved (Tmax), and the area under the plasma concentration-time curve (AUC) were also determined.Results: The highest concentration and widest AUC of AnxA1 were obtained in MP innovator drug. MP innovator and branded generic reaches the peak time (Tmax) at the third 3rd h, while the MP generic reaches the peak time at the 5th h. The results showed that there was no significant difference in the serum concentration of AnxA1 between MP tablets after analyzed with a one-way analysis of variance.Conclusion: It could be concluded that the innovator drug of MP tablet gave the same effect on the serum concentration of AnxA1 than its generic counterparts, but an onset of action MP innovator and branded generic is faster than the generic product.

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