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Κυριακή 29 Μαΐου 2022

Plasma trough concentration distribution and safety of high‐dose teicoplanin for patients with augmented renal clearance

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Plasma trough concentration distribution and safety of high-dose teicoplanin for patients with augmented renal clearance

Teicoplanin plasma trough concentration (C min) and probability rates of C min > 10 mg/L in the augmented renal clearance (ARC) and non-ARC groups on the third day of medication (day 3) and during the dose maintenance period. After the HD, plasma samples were collected before the third day of medication. The teicoplanin C min values in the ARC and non-ARC groups were 17.3 ± 9.2 mg/L and 15.5 ± 7.9 mg/L, respectively (p = 0.663) (Figure A). The probability rate of C min > 10 mg/L also did not differ significantly between the two groups (85.7% [6/7] vs. 60.0% [6/10], p = 0.338, Figure C). During the dose maintenance period (3 days after medication), the teicoplanin C min was significantly lower in ARC group than in the non-ARC group (18.3 ± 5.1 mg/L vs. 25.5 ± 11.9 mg/L, p = 0.016, Figure A), while there was no significant difference in the probability rate of C min > 10 mg/L between the two groups (90.0% [9/10] vs. 96.2% [25/26], p = 0.484, Figure C). After the LD, plasma samples were collected before the third day of medication. The teicoplanin C min values in the ARC and non-ARC groups were 6.8 ± 3.9 mg/L and 7.9 ± 3.1 mg/L, respectively (p = 0.585) (Figure B). The probability rate of C min > 10 mg/L did not differ significantly between the two groups (20.0% [1/5] vs. 11.1% [1/9], p = 1.000, Figure D). During the dose maintenance period, the teicoplanin C min values in the ARC and non-ARC groups were 12.2 ± 6.3 mg/L and 13.0 ± 4.6 mg/L, respectively (p = 0.713) (Figure B). The probability rate of C min > 10 mg/L was 61.5% (8/13) in both groups (Figure D). It should be noted that on the third day of medication, the HD group had a significantly higher teicoplanin C min than the LD group for ARC (17.3 ± 9.2 mg/L vs. 6.8 ± 3.9 mg/L, p = 0.039, Figure A and B), but there was no significant intergroup difference in the probability rates of C min > 10 mg/L (85.7% [6/7] vs. 20.0% [1/5], p = 0.072, Figures C and D). During the dose maintenance period, the teicoplanin C min was significantly higher in the HD group than in the LD group for ARC (18.3 ± 5.1 mg/L vs. 12.2 ± 6.3 mg/L, p = 0.022, Figures A and B), while there was no significant intergroup difference in their probability rates of C min > 10 mg/L (90.0% [9/10] vs. 61.5% [8/13], p = 0.179, Figures C and D). Notes: A, HD; B, LD; C, HD; D, LD; *p < 0.05.


Abstract

What Is Known and Objective

There are few reports on the distribution of the plasma trough concentration (C min) of teicoplanin in patients with augmented renal clearance (ARC) and on the safety of a high-dose regimen (HD; 800 mg loading dose for q12h three times followed by an 800 mg qd maintenance dose). The objective of this study was to determine the C min values of teicoplanin in ARC patients using HD teicoplanin to provide a reference for individualized medication.

Methods

Data on patients treated with teicoplanin from January 2019 to January 2021 were collected retrospectively and divided into ARC (creatinine clearance rate [CCr] >130 ml/min, n = 22) and non-ARC (60 ml/min ≤ CCr ≤130 ml/min, n = 24) groups. The C min values in the two patient groups were analysed during the HD and the low-dose regimen (LD; all other regimens) on the third day of medication and during the dose maintenance period. Liver and kidney function indexes were also analysed before and after medication.

Results and Discussions

On the third day of the HD, C min did not differ significantly between the ARC and non-ARC groups (17.3 ± 9.2 mg/L [mean ± SD] vs. 15.5 ± 7.9 mg/L, p = 0.663), while C min in the ARC group was significantly lower for the LD (6.8 ± 3.9 mg/L, p = 0.039). During the dose maintenance period, C min in the ARC group when receiving the HD (18.3 ± 5.1 mg/L) was significantly lower than that in the non-ARC group (25.5 ± 11.9 mg/L, p = 0.016) and significantly higher than that for the LD (12.2 ± 6.3 mg/L, p = 0.022). Nephrotoxicity and hepatotoxicity incidence rates did not differ significantly between these groups.

What Is New and Conclusion

These results suggest that it is necessary to apply a loading dose of 800 mg (but not higher) q12h three times for patients with ARC, with 800 mg needed as a maintenance dose during severe infection, and 600 mg or 400 mg for mild infection.

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