case_images: PMC9411638_01
case_images: Family genogram for RYR1 (NM 001042723) mutations. The patient's mother and third sister were confirmed to have homologous gene mutations, while his father as well as eldest sister and second sister did not find the same mutations in genetic testing.
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case_images: PMC9411638_01_fmed-09-918245-g001.jpg
case_images: F1
case_images: Subsequent genetic testing revealed mutations on RYR1 (NM 001042723) c.11120A > G and c.12227C > T (Figure 1).
case_images: The goodness of fit between predicted and measured dantrolene plasma concentration (ng/ml). According to the Malignant Hyperthermia Association of the United States (MHAUS) guidelines (2.5 mg/kg as the first bolus and followed by 1 mg/kg bolus every 6 h), predicted concentrations of dantrolene were calculated with the reported population PK model and didn't match well with the measured concentrations over the entire concertation range after PE. PE, plasma exchange; PK, pharmacokinetics.
case_images: fmed-09-918245-g002.jpg
case_images: PMC9411638_01_fmed-09-918245-g002.jpg
case_images: F2
case_images: However, the predictions matched with the measured values only nearby the lower limit, suggesting new pharmacokinetic parameters for dantrolene should be estimated, which might be more suitable for MH adolescents (Figure 2).
case_images: Measured dantrolene plasma concentration (dots) during PE and renal clearance period. Under the hypotheses of invariable renal function, pharmacokinetic parameters calculated from 4 to 16 h (after PE, only with renal clearance) was applied to stimulate AUC in the first 4 h for dantrolene. The eliminated dantrolene during the first 4 h was 27,420 ng*h/mL with PE, while decreased to 27,302 ng*h/mL if without PE. PE, plasma exchange; AUC, area under the curve.
case_images: fmed-09-918245-g003.jpg
case_images: PMC9411638_01_fmed-09-918245-g003.jpg
case_images: F3
case_images: The renal CL estimate for dantrolene was 0.33 mL/(min*kg) and Vd was 0.51 L/kg, the details were shown in Table 1 and Figure 3.