Age- and Bodyweight-dependent Allometric Exponent Model for Scaling Clearance and Maintenance Dose of Theophylline From Neonates to Adults

SummaryDue to large inter-individual variations, the dose of vitamin K antagonist required to target the desired hypocoagulability is hardly predictible for a given patient, and the time needed to reach therapeutic equilibrium may be excessively long. This work reports on a simple method for predicting the daily maintenance dose of fluindione after the third intake. In a first step, 37 patients were delivered 20 mg of fluindione once a day, at 6 p.m. for 3 consecutive days. On the morning of the 4th day an INR was performed. During the following days the dose was adjusted to target an INR between 2 and 3. There was a good correlation (r = 0.83, p<0.001) between the INR performed on the morning of day 4 and the daily maintenance dose determined later by successive approximations. This allowed us to write a decisional algorithm to predict the effective maintenance dose of fluindione from the INR performed on day 4. The usefulness and the safety of this approach was tested in a second prospective study on 46 patients receiving fluindione according to the same initial scheme. The predicted dose was compared to the effective dose soon after having reached the equilibrium, then 30 and 90 days after. To within 5 mg (one quarter of a tablet), the predicted dose was the effective dose in 98%, 86% and 81% of the patients at the 3 times respectively. The mean time needed to reach the therapeutic equilibrium was reduced from 13 days in the first study to 6 days in the second study. No hemorrhagic complication occurred. Thus the strategy formerly developed to predict the daily maintenance dose of warfarin from the prothrombin time ratio or the thrombotest performed 3 days after starting the treatment may also be applied to fluindione and the INR measurement.

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Predicting the Dose of Warfarin for Therapeutic Anticoagulation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657174 ◽

1982 ◽

Vol 47 (03) ◽

pp. 230-231 ◽

Cited By ~ 8

Author(s):

N K Sharma ◽

P A Routledge ◽

M D Rawlins ◽

D M Davies

Keyword(s):

Therapeutic Range ◽

Significant Relationship ◽

Maintenance Dose ◽

Warfarin Dose ◽

Loading Dose ◽

Intravenous Injections ◽

Therapeutic Anticoagulation ◽

Close Relationship ◽

The Relationship ◽

Anticoagulant Response

SummaryThe validity of a previously described technique for predicting warfarin requirements based on the anticoagulant response to a fixed loading dose was assessed prospectively in 57 patients. There was a close relationship between the predicted and initially observed daily warfarin dose required to maintain the patient within the therapeutic range for anticoagulation. The significant relationship between predicted and observed maintenance dose persisted at 4 and 12 weeks although it decreased with increasing time.The relationship between observed and predicted maintenance requirement of warfarin was not affected by the concomitant use of intermittent intravenous injections of heparin when 9 hr was allowed to elapse between the previous dose of heparin and the thrombotest estimation on which the prediction was based.It is concluded that the method is valuable in predicting an individual’s warfarin requirement, although it does not obviate the need for regular monitoring of anticoagulant control.

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LOwer Maintenance Dose TICagrelor in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention

Case Medical Research ◽

10.31525/ct1-nct04060914 ◽

2019 ◽

Author(s):

Keyword(s):

Percutaneous Coronary Intervention ◽

Acute Coronary Syndrome ◽

Maintenance Dose ◽

Coronary Intervention ◽

Coronary Syndrome ◽

Percutaneous Coronary

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Faculty Opinions recommendation of The allometric exponent for scaling clearance varies with age: a study on seven propofol datasets ranging from preterm neonates to adults.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727243275.793527927 ◽

2017 ◽

Author(s):

Anne M Lynn

Keyword(s):

Preterm Neonates ◽

Allometric Exponent

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COMPUTER PREDICTION OF ANTICOAGULATION STATUS AND WARFARIN DOSE FOLLOWING CARDIAC SURGERY

10.1055/s-0038-1643275 ◽

1987 ◽

Author(s):

M J Crow ◽

A B Latif ◽

A I Critchley ◽

C Stainton ◽

P Nealon ◽

...

Keyword(s):

Therapeutic Range ◽

Maintenance Dose ◽

Prosthetic Heart Valve ◽

Warfarin Dose ◽

Study Data ◽

Computer Prediction ◽

Prothrombin Activity ◽

Upper Limit ◽

Post Operative Period ◽

Post Operation

Fluctuations are freguently seen in the anticoagulant status of patients in the immediate post operative period following prosthetic heart valve replacement. These patients are at high risk of haemorrhage or thromboembolism. We have used a pharmokinetic model of warfarin metabolism to develop a computer programme to predict the maintenance dose of warfarin from early prothrombin activity determinations. This will enable controlled anticoagulation to be achieved. The expression for warfarin kinetics employs 4 constants determined by the residual sum of the sguares, which are used immediately to redefine dosage predictions. In a pilot study data obtained from 16 patients post operation 3, 5 and 7 days after commencing treatment, has been used to predict the reguired maintenance dose at 21 days. These predicted doses were then compared with the maintenance dose achieved by clinical practice. The programme was told to optimise its dose to achieve a PT ratio of 3 whereas clinically the ratio was allowed to vary in the therapeutic range of 2 to 4. Predicted doses at 21 days are shown.in the table:Correlation between predicted and clinical maintenance doses after 3 and 5 days treatment was poor but had improved significantly by 7 days, despite similar levels of prothrombin activity. Predicted prothrombin activity never exceeded the upper limit of the therapeutic range, and the predicted dose can be uprated on addition of further data within 2 minutes.After 7 days computer predicted warfarin dose has produced a good correlation with the clinical maintenance dose (the doses of only 3 patients varying by more than 1 mg/day). The significant fluctuations seen in the prothrombin ratio during clinical dosage were not observed with computer dosing and we now feel it is safe to use this programme to anticoagulate patients post operatively.

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295 First-in-human Phase I trial of IBI188, an anti-CD47 targeting monoclonal antibody, in patients with advanced solid tumors and lymphomas

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0295 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A322-A322

Author(s):

Nehal Lakhani ◽

Marlana Orloff ◽

Siqing Fu ◽

Ying Liu ◽

Yan Wang ◽

...

Keyword(s):

Monoclonal Antibody ◽

T Cells ◽

Solid Tumors ◽

Dose Level ◽

Maintenance Dose ◽

Receptor Occupancy ◽

Priming Dose ◽

Dose Escalation Study ◽

Optimal Maintenance ◽

Grade 3

BackgroundIBI188 is a humanized IgG4 monoclonal antibody targeting CD47, an antiphagocytic (‘don’t eat me’) signal present on cancer cells. Blockage of this myeloid checkpoint, IBI188 enhances tumor cell phagocytosis and cross priming of T-cells. We conducted a first-in-human phase 1a trial to evaluate the tolerability, safety and PK/PD characteristics of IBI188. (NCT03763149).MethodsPatients with advanced/refractory solid tumors or lymphoma were enrolled in this two-part dose-escalation study: Part A for testing optimal priming doses at 0.1, 0.3, and 1 mg/kg and Part B for optimal maintenance doses at 3, 10, 20, 30 mg/kg weekly. An accelerated titration followed by traditional 3+3 design was used in this study with a 28-day dose-limiting toxicity (DLT) observation period. Primary endpoint was safety profile; secondary endpoints included PK parameters and PD markers, i.e. CD47 receptor occupancy.ResultsAs of June 18, 2020, 20 patients have been enrolled, 6 in Part A and 14 in Part B. There was no DLT reported at any dose level. The median treatment duration was 1.8 months (0.2–5.5) months. The most common treatment-related adverse events (TRAEs) were nausea (n=7), back pain (n=7), fatigue (n=6), vomiting (n=4) and blood bilirubin increased (n=4). Three patients had ≥ Grade 3 TRAEs (Grade 3 blood bilirubin increase, Grade 4 platelet count decrease and Grade 3 anemia, each in 1 patient). Three of 20 patients (15%) had anemia, an expected TRAE associated with the mechanism of IBI188. Majority of the patients (65%) had infusion related reactions (IRR). All IRRs were Grade 1–2 and able to be managed with standard IRR treatment. The clearance of IBI188 decreased with the increasing dose from 3 to 20 mg/kg and IBI188 can overcome the sink at 10 mg/kg or higher dose level. The PK analysis at 30 mg/kg is ongoing. The 10 mg/kg maintenance dose resulted in T cells receptor occupancy above 80%. After multiple administrations (≥ 3 times, including the priming dose), the RBC and T cells receptor occupancy tends to be stable and maintained around 90%. The receptor occupancy analysis at 20 mg/kg and 30 mg/kg is ongoing.ConclusionsIBI188 was well tolerated at 1 mg/kg priming dose following by the maintenance dose up to 30 mg/kg.Trial RegistrationNCT03763149

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Effects of Creatine Monohydrate Supplementation During Combined Strength and High Intensity Rowing Training on Performance

Canadian Journal of Applied Physiology ◽

10.1139/h01-029 ◽

2001 ◽

Vol 26 (6) ◽

pp. 527-542 ◽

Cited By ~ 24

Author(s):

Daniel G. Syrotuik ◽

Alex B. Game ◽

Ellen M. Gillies ◽

Gordon J. Bell

Keyword(s):

Body Composition ◽

Resistance Training ◽

High Intensity ◽

Maintenance Dose ◽

Creatine Monohydrate ◽

Training Volume ◽

Placebo Condition ◽

Strength Performance ◽

Composition Formula ◽

Training Interval

This study investigated the effect of creatine monohydrate (Cr) supplementation on performance and training volume in rowers. Twenty-two rowers trained with continuous and interval rowing and resistance training 4 and 2 days/week, respectively, for 6 weeks. Cr supplementation consisted of a 5-day load (0.3 g/kg−1•day−1) followed by a 5-week maintenance dose (0.03 g/kg−1•day−1) while training. Five days of Cr loading did not change body composition, repeated interval rowing performance, 2,000-m rowing times, or strength performance. Five additional weeks of training with a maintenance dose of Cr or placebo significantly improved body composition, [Formula: see text] 2,000-m rowing times, repeated power interval performance, and strength to a similar extent in both groups. Subjects training with Cr did not perform more repetitions per set of strength exercise nor produce or maintain higher power outputs during repeated rowing sessions. Cr supplementation did not increase performance or training volume over a placebo condition in rowers that performed a combined high intensity rowing and strength program. Key Words: ergogenic, anaerobic, resistance training, interval training

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