| Title |
Pharmacometric and Electrocardiographic Evaluation of Chloroquine and Azithromycin in Healthy Volunteers
|
|---|---|
| Published in |
Clinical Pharmacology & Therapeutics, June 2022
|
| DOI | 10.1002/cpt.2665 |
| Pubmed ID | |
| Authors |
Palang Chotsiri, Joel Tarning, Richard M. Hoglund, James A. Watson, Nicholas J. White |
| Abstract |
Chloroquine and azithromycin were developed in combination for the preventive treatment of malaria in pregnancy, and more recently were proposed as COVID-19 treatment options. Billions of doses of chloroquine have been administered worldwide over the past 70 years but concerns regarding cardiotoxicity, notably the risk of torsades de pointes (TdP), remain. This investigation aimed to characterize the pharmacokinetics and electrocardiographic effects of chloroquine and azithromycin observed in a large previously conducted healthy volunteer study. Healthy adult volunteers (n = 119) were randomized into five arms: placebo, chloroquine alone (600 mg base), or chloroquine with either 500 mg, 1000 mg, or 1500 mg of azithromycin all given daily for three days. Chloroquine and azithromycin levels, measured using LC-MS/MS, and electrocardiograph intervals were recorded at frequent intervals. Time-matched changes in the PR, QRS, and heart rate-corrected JTc, and QTc intervals were calculated and the relationship with plasma concentrations was evaluated using linear and nonlinear mixed-effects modeling. Chloroquine and azithromycin pharmacokinetics were described satisfactorily by two- and three-compartment distribution models, respectively. No drug-drug interaction between chloroquine and azithromycin was observed. Chloroquine resulted in concentration-dependent prolongation of the PR, QRS, and JTc intervals with a minimal additional effect of azithromycin. QRS widening contributed approximately 28% of the observed QT prolongation. Chloroquine causes significant concentration-dependent delays in both ventricular depolarization and repolarization. Coadministration of azithromycin did not significantly increase these effects. The arrhythmogenic risk of TdP associated with chloroquine may have been substantially overestimated in studies which did not separate electrocardiograph QRS and JT prolongation. |
X Demographics
The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 29% |
| Unknown | 5 | 71% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 6 | 86% |
| Practitioners (doctors, other healthcare professionals) | 1 | 14% |
Mendeley readers
The data shown below were compiled from readership statistics for 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 27 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Unspecified | 5 | 19% |
| Student > Ph. D. Student | 4 | 15% |
| Student > Doctoral Student | 3 | 11% |
| Student > Bachelor | 2 | 7% |
| Student > Master | 2 | 7% |
| Other | 2 | 7% |
| Unknown | 9 | 33% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 30% |
| Design | 5 | 19% |
| Veterinary Science and Veterinary Medicine | 1 | 4% |
| Nursing and Health Professions | 1 | 4% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
| Other | 2 | 7% |
| Unknown | 9 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 September 2022.
All research outputs
#3,904,702
of 23,989,432 outputs
Outputs from Clinical Pharmacology & Therapeutics
#777
of 4,320 outputs
Outputs of similar age
#79,144
of 429,333 outputs
Outputs of similar age from Clinical Pharmacology & Therapeutics
#11
of 46 outputs
Altmetric has tracked 23,989,432 research outputs across all sources so far. Compared to these this one has done well and is in the 83rd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,320 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one has done well, scoring higher than 81% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 429,333 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 81% of its contemporaries.
We're also able to compare this research output to 46 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 78% of its contemporaries.