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.

Influence of cimetidine on the toxicity and toxicokinetics of diazinon in the rat

1996 ◽  
Vol 15 (5) ◽  
pp. 391-395 ◽  
Author(s):  
HX Wu ◽  
CI Evreux-Gros ◽  
J. Descotes
Keyword(s):  
Wistar Rats ◽  
Total Body Clearance ◽  
Systemic Circulation ◽  
Time Curve ◽  
Concentration Time ◽  
Male Wistar Rats ◽  
Total Body ◽  
The Brain ◽  
Brain Acetylcholinesterase ◽  
Body Clearance

1 The influence of cimetidine on diazinon toxicity and toxicokinetics was investigated in male Wistar rats. 2 The acute toxicity of diazinon, as well as brain acetylcholinesterase and carboxylesterase inhibition, were potentiated by pretreating rats with cimetidine (80 mg kg-1, ip) 1 and 24 h prior to diazinon applica tion (50 mg kg-1, i.p.). 3 Comparison of toxicokinetic parameters between control and cimetidine-treated animals, showed a significant decrease in diazinon total body clearance and a marked increase in the area under the plasma concentration-time curve following cimetidine. 4 These results indicate that a major cause of the potentiation of diazinon may be related to the increase in the amount of diazinon in the systemic circulation as well as in the brain.

scholarly journals Pharmacokinetic evaluation of the interaction between oral kaempferol and ethanol in rats

2016 ◽  
Vol 66 (4) ◽  
pp. 563-568 ◽  
Author(s):  
Zhaoxiang Zhou ◽  
Meng Wang ◽  
Zengjun Guo ◽  
Xiaoying Zhang
Keyword(s):  
Oral Bioavailability ◽  
High Performance ◽  
Total Body Clearance ◽  
Control Groups ◽  
Oral Gavage ◽  
Time Curve ◽  
Concentration Time ◽  
Oral Control ◽  
Total Body ◽  
Body Clearance

Abstract This study was aimed at investigating the effect of ethanol on oral bioavailability of kaempferol in rats, namely, at disclosing their possible interaction. Kaempferol (100 or 250 mg kg-1 bm) was administered to the rats by oral gavage with or without ethanol (600 mg kg-1 bm) co-administration. Intravenous administration (10 and 25 mg kg-1 bm) of kaempferol was used to determine the bioavailability. The concentration of kaempferol in plasma was estimated by ultra high performance liquid chromatography. During coadministration, a significant increase of the area under the plasma concentration-time curve as well as the peak concentration were observed, along with a dramatic decrease in total body clearance. Consequently, the bioavailability of kaempferol in oral control groups was 3.1 % (100 mg kg-1 bm) and 2.1 % (250 mg kg-1 bm). The first was increased by 4.3 % and the other by 2.8 % during ethanol co-administration. Increased permeability of cell membrane and ethanolkaempferol interactions on CYP450 enzymes may enhance the oral bioavailability of kaempferol in rats.

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.

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 Fosamprenavir plus Ritonavir Increases Plasma Ketoconazole and Ritonavir Exposure, while Amprenavir Exposure Remains Unchanged

2007 ◽  
Vol 51 (8) ◽  
pp. 2982-2984 ◽  
Author(s):  
Mary B. Wire ◽  
Charles H. Ballow ◽  
Julie Borland ◽  
Mark J. Shelton ◽  
Yu Lou ◽  
...  
Keyword(s):  
Steady State ◽  
Healthy Subjects ◽  
Open Label ◽  
Time Curve ◽  
Once Daily ◽  
Open Label Study ◽  
Label Study ◽  
Concentration Time

ABSTRACT Plasma ketoconazole (KETO), amprenavir (APV), and ritonavir (RTV) pharmacokinetics were evaluated in 15 healthy subjects after being treated with KETO at 200 mg once daily (QD), fosamprenavir (FPV)/RTV at 700/100 mg twice daily (BID), and then KETO at 200 mg QD plus FPV/RTV at 700/100 mg BID in this open-label study. The KETO area under the concentration-time curve at steady state was increased 2.69-fold with FPV/RTV. APV exposure was unchanged, and RTV exposure was slightly increased.

scholarly journals Single-Dose Pharmacokinetics of Meropenem during Continuous Venovenous Hemofiltration

1998 ◽  
Vol 42 (9) ◽  
pp. 2417-2420 ◽  
Author(s):  
Florian Thalhammer ◽  
Peter Schenk ◽  
Heinz Burgmann ◽  
Ibrahim El Menyawi ◽  
Ursula M. Hollenstein ◽  
...  
Keyword(s):  
High Performance ◽  
Peak Plasma ◽  
Continuous Venovenous Hemofiltration ◽  
Drug Concentrations ◽  
Elimination Half ◽  
Pharmacokinetic Properties ◽  
Severe Infections ◽  
Total Body ◽  
Trough Levels ◽  
Body Clearance

ABSTRACT The pharmacokinetic properties of meropenem were investigated in nine critically ill patients treated by continuous venovenous hemofiltration (CVVH). All patients received one dose of 1 g of meropenem intravenously. High-flux polysulfone membranes were used as dialyzers. Meropenem levels were measured in plasma and ultrafiltrate by high-performance liquid chromatography. The total body clearance and elimination half-life were 143.7 ± 18.6 ml/min and 2.46 ± 0.41 h, respectively. The post- to prehemofiltration ratio of meropenem was 0.24 ± 0.06. Peak plasma drug concentrations measured 60 min postinfusion were 28.1 ± 2.7 μg/ml, and trough levels after 6 h of CVVH were 6.6 ± 1.5 μg/ml. The calculated total daily meropenem requirement in these patients with acute renal failure and undergoing CVVH was 2,482 ± 321 mg. Based on these data, we conclude that patients with severe infections who are undergoing CVVH can be treated effectively with 1 g of meropenem every 8 h.

scholarly journals Administration of aminoglycosides to hemodialysis patients immediately before dialysis: a new dosing modality.

1997 ◽  
Vol 41 (12) ◽  
pp. 2597-2601 ◽  
Author(s):  
H Matsuo ◽  
J Hayashi ◽  
K Ono ◽  
K Andoh ◽  
Y Andoh ◽  
...  
Keyword(s):  
High Performance ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Cellulose Triacetate ◽  
The Body ◽  
High Rate ◽  
Complete Disappearance ◽  
Time Curve ◽  
Once Daily ◽  
Ethylene Vinyl Alcohol ◽  
Concentration Time

We describe a new modality for administering aminoglycosides to hemodialysis (HD) patients, namely, a modification of the once-daily regimen which consists of administering the aminoglycosides over 60 min by drip infusion just before each HD session, with a preplanned peak concentration being reached at the beginning of the session and then with a rapidly decreasing concentration being achieved by the start of HD. The area under the concentration-time curve (AUC), i.e., the accumulation of the drug in the body, is thus minimized by this modality. Arbekacin (ABK) was given at a dose of 2 mg/kg of body weight to 10 HD patients infected with methicillin-resistant Staphylococcus aureus (MRSA) for 2 weeks (six sessions in total), resulting in the complete disappearance of MRSA in 5 patients. A high rate of elimination of ABK was attained for each patient while the patient was on HD (range, 0.20 to 0.42 h-1; mean 0.28 +/- 0.08 h-1) by using high-performance dialyzers provided with membranes made of either polymethylmethacrylate, cellulose triacetate (CTA), or ethylene vinyl alcohol. The best results were obtained with the CTA membrane, as revealed by the overall mass transfer coefficient (Ko). The AUC in the simulation model for the variation in the serum ABK concentration in this modality was calculated to be 40% of that of the conventional post-HD dosing modality, suggesting that a much higher dose could be administered to HD patients who receive HD thrice weekly (4 h per session), giving, e.g., 4 mg/kg initially and before the HD sessions, when there is an interval of 68 h from HD session to HD session, and giving 2 mg/kg before the other sessions.

scholarly journals Slower Elimination of Tofacitinib in Acute Renal Failure Rat Models: Contribution of Hepatic Metabolism and Renal Excretion

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 714
Author(s):  
Sung Hun Bae ◽  
Sun-Young Chang ◽  
So Hee Kim
Keyword(s):  
Rheumatoid Arthritis ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Hepatic Metabolism ◽  
Term Treatment ◽  
Concentration Time ◽  
Long Term Treatment ◽  
Total Body ◽  
Body Clearance

Tofacitinib is a Jak inhibitor developed as a treatment for rheumatoid arthritis. Tofacitinib is metabolized mainly through hepatic CYP3A1/2, followed by CYP2C11. Rheumatoid arthritis tends to increase renal toxicity due to drugs used for long-term treatment. In this study, pharmacokinetic changes of tofacitinib were evaluated in rats with gentamicin (G-ARF) and cisplatin-induced acute renal failure (C-ARF). The time-averaged total body clearance (CL) of tofacitinib in G-ARF and C-ARF rats after 1-min intravenous infusion of 10 mg/kg was significantly decreased by 37.7 and 62.3%, respectively, compared to in control rats. This seems to be because the time-averaged renal clearance (CLR) was significantly lower by 69.5 and 98.6%, respectively, due to decreased creatinine clearance (CLCR). In addition, the time-averaged nonrenal clearance (CLNR) was also significantly lower by 33.2 and 57.4%, respectively, due to reduction in the hepatic CYP3A1/2 and CYP2C11 subfamily in G-ARF and C-ARF rats. After oral administration of tofacitinib (20 mg/kg) to G-ARF and C-ARF rats, both CLR and CLNR were also significantly decreased. In conclusion, an increase in area under plasma concentration-time curves from time zero to time infinity (AUC) of tofacitinib in G-ARF and C-ARF rats was due to the significantly slower elimination of tofacitinib contributed by slower hepatic metabolism and urinary excretion of the drug.

scholarly journals Once-Daily Dosing in Dogs Optimizes Daptomycin Safety

2000 ◽  
Vol 44 (11) ◽  
pp. 2948-2953 ◽  
Author(s):  
F. B. Oleson ◽  
C. L. Berman ◽  
J. B. Kirkpatrick ◽  
K. S. Regan ◽  
J.-J. Lai ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Maximum Concentration ◽  
Time Curve ◽  
Once Daily ◽  
Gram Positive Bacteria ◽  
Concentration Time ◽  
Serum Creatine Phosphokinase ◽  
Lower Maximum ◽  
Resistant Strains ◽  
Lipopeptide Antibiotic

ABSTRACT Daptomycin is a novel lipopeptide antibiotic with potent bactericidal activity against most clinically important gram-positive bacteria, including resistant strains. Daptomycin has been shown to have an effect on skeletal muscle. To guide the clinical dosing regimen with the potential for the least effect on skeletal muscle, two studies were conducted with dogs to compare the effects of repeated intravenous administration every 24 h versus every 8 h for 20 days. The data suggest that skeletal-muscle effects were more closely related to the dosing interval than to either the maximum concentration of the drug in plasma or the area under the concentration-time curve. Both increases in serum creatine phosphokinase activity and the incidence of myopathy observed at 25 mg/kg of body weight every 8 h were greater than those observed at 75 mg/kg every 24 h despite the lower maximum concentration of drug in plasma. Similarly, the effects observed at 25 mg/kg every 8 h were greater than those observed at 75 mg/kg every 24 h at approximately the same area under the concentration-time curve from 0 to 24 h. Once-daily administration appeared to minimize the potential for daptomycin-related skeletal-muscle effects, possibly by allowing for more time between doses for repair of subclinical effects. Thus, these studies with dogs suggest that once-daily dosing of daptomycin in humans should have the potential to minimize skeletal-muscle effects. In fact, interim results of ongoing clinical trials, which have focused on once-daily dosing, appear to be consistent with this conclusion.

scholarly journals Pharmacokinetics of Tedizolid in an Obese Patient after Bariatric Surgery

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Matthieu Grégoire ◽  
Julia Brochard Libois ◽  
Denis Waast ◽  
Benjamin Gaborit ◽  
Marc Dauty ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Bypass Surgery ◽  
Obese Woman ◽  
Total Plasma ◽  
Time Curve ◽  
Once Daily ◽  
Content Type ◽  
Concentration Time ◽  
Target Ratio ◽  
Plasma Peak

ABSTRACT An obese woman was treated with oral tedizolid 200 mg once daily for pseudoarthrosis 10 years after Roux-en-Y bypass surgery. Total plasma peak concentration was 2.12 mg/liter 3 h after intake, and area under the concentration-time curve from 0 to 24 h (AUC 0–24 ) was 28.3 mg/liter · h. The AUC 0–24 /MIC ratio for unbound concentrations and for sensitive Staphylococcus and Streptococcus strains was ≥10.8, higher than the target ratio of 3. These results support the use of tedizolid without adjustment after bariatric surgery.

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