Session Information
Session Type: Poster Session (Tuesday)
Session Time: 9:00AM-11:00AM
Background/Purpose: A low glomerular filtration rate (GFR: < 60 mL/min/1.73 m2) is an established risk of hydroxychloroquine (HCQ) retinopathy and is presumably related to higher HCQ concentrations. However, the pharmacokinetics of HCQ in impaired renal function are not known. Herein, we evaluated the pharmacokinetics of HCQ in systemic lupus erythematosus (SLE) patients with renal insufficiency using single-dose and population pharmacokinetic analysis.
Methods: The present study was conducted in both the in-patient and out-patient settings at three hospitals and enrolled 20 SLE patients with various degrees of renal impairment. An HCQ dose of 300 mg/d (one 200 mg tablet and 100 mg of crushed HCQ) based on 6.5 mg/IBW was administered. Nine whole blood samples were collected from inpatients, and fewer samples were collected from outpatients from the pre-dose period up to 72 hours post-dose for single-dose pharmacokinetic analysis, and four to six blood samples after at least 16 weeks starting HCQ were collected from outpatients for population pharmacokinetics. The HCQ concentrations were measured using a validated LC/MS/MS. The pharmacokinetic parameters were estimated by the two-compartment model. The area under the blood concentration-time curve (AUC) was analyzed using moment analysis if five or more samples were collected for single-dose pharmacokinetic analysis. Population pharmacokinetics were analyzed by computer using a non-linear mixed-effects model.
Results: One patient was excluded from analysis due to malabsorption syndrome. Six patients with GFR >60 mL/min/1.73 m2, eight patients with GFR 45-59 mL/min/1.73 m2, and five patients with GFR 15-44 mL/min/1.73 m2 were included. The patient background is shown in Table 1. The dosage based on actual body weight and body habitus was similar between groups. The pharmacokinetic parameters are summarized in Table 2. In total, 185 HCQ concentration measurements were obtained from 19 patients.
There was a trend towards increased AUC, decreased renal elimination, and prolonged elimination half-life in patients with moderately impaired renal function. In population pharmacokinetics, HCQ clearance tended to be influenced by renal function.
Table 1. Patient demographics
|
|
eGFR (ml/min/1.73 m2) |
||
|
-44 |
45-59 |
60- |
|
|
N |
5 |
8 |
6 |
|
No. of blood samples |
45 |
70 |
70 |
|
Age |
56.8 (6.8) |
50.5 (13.8) |
37.5 (8.6) |
|
Cr (mg/dl) |
1.45 (0.25) |
0.92 (0.09) |
0.66 (0.06) |
|
eGFR (ml/min) |
34.8 (5.6) |
51.6 (3.9) |
81.8 (11.9) |
|
BMI |
21.6 (6.0) |
21.7 (2.0) |
21.3 (5.0) |
|
Dose/IBW (mg/kg) |
5.6 (0.5) |
6.1 (0.4) |
5.6 (0.3) |
|
Dose/ABW (mg/kg) |
5.7 (1.5) |
5.6 (0.5) |
5.5 (0.9) |
Numbers represent the mean (SD).
Table 2. Pharmacokinetic parameters
|
|
eGFR (ml/min) |
||
|
-44 |
45-59 |
60- |
|
|
C1max (μg/ml) |
0.26 (0.09) |
0.33 (0.21) |
0.31 (0.12) |
|
Tmax (h) |
3.8 (0.45) |
2.6 (1.1) |
3.2 (1.3) |
|
AUC (μg/mL･hr) |
10.9 (3.2) *1 |
10.7 (2.3) *2 |
7.6 (2.6) *3 |
|
Css (μg/ml) |
0.98 (0.29) |
1.03 (0.36) |
0.76 (0.20) |
|
CL/F（L/h) |
11.5 (4.0) |
12.2 (7.6) |
16.2 (6.8) |
|
T1/2 (h) |
16.9 (14.2) |
20.6 (19.9) |
10.8 (7.8) |
Numbers represent the mean (SD).
*1: n=2, *2: n=4, *3: n=5
Conclusion: Adjusting the HCQ dosage may be warranted in patients with moderately impaired renal function.
To cite this abstract in AMA style:
Yokogawa N, Hashiguchi M, Nagai Y, Shimada K, Sugii S, Oshima M, Setoguchi K, Shimizu M. Pharmacokinetics of Hydroxychloroquine in Systemic Lupus Erythematosus Patients with Renal Impairment [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/pharmacokinetics-of-hydroxychloroquine-in-systemic-lupus-erythematosus-patients-with-renal-impairment/. Accessed .« Back to 2019 ACR/ARP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/pharmacokinetics-of-hydroxychloroquine-in-systemic-lupus-erythematosus-patients-with-renal-impairment/