Pharmacokinetic/pharmacodynamic study of posaconazole delayed-release tablet in a patient with coexisting invasive aspergillosis and mucormycosis

Figures & data

Figure 1 Posaconazole plasma concentration on days 1, 7, 14, and 35 in a patient with coexisting invasive aspergillosis and mucormycosis.

Table 1 Pharmacokinetic parameters on day 1 after loading dose of 300 mg twice daily, on day 7 and day 14 after maintenance dose of 400 mg once daily, and 300 mg once daily on day 35

Dose	Day	Cmin (mg/L)	AUC0-t (h·mg/L)	AUC0-∞ (h·mg/L)	Cavg (mg/L)	Cmax (mg/L)	Tmax (hrs)	T1/2 (hrs)	CL/F (L/hrs)	Vd/F (L)
300 mg q 12 hrs	1	0.57 (at 12 hrs)	8.15 (at 12 hrs)	20.90	0.68 (at 12 hrs)	0.88 (at 12 hrs)	2.0	15.42	14.35	319.70
		1.78 (at 24 hrs)	16.30 (at 24 hrs)		1.36 (at 24 hrs)
400 mg q 24 hrs	7	2.48	76.18	179.20	3.17	3.92	6.0	28.80	5.25	217.87
400 mg q 24 hrs	14	2.59	77.46	201.28	3.23	3.81	6.0	33.16	5.16 9	247.08
300 mg q 24 hrs	35	1.54	49.23	129.29	2.05	3.18	2.0	35.97	6.09	315.74

Abbreviations: C_min, minimum plasma concentration (C_min on day 1 was determined at 12 hrs before next dose on day 1; however, on days 7, 14, and 35, the C_min was determined at 24 hrs before next dose to be given the next day); AUC_0-t, area under concentration-time curve from time zero to time of the last quantifiable sample (time of the last quantifiable sample was 12 hrs on day 1, and 24 hrs on days 7, 14, and 35); AUC_0-∞, area under concentration-time curve from time zero to infinity; C_avg, average concentration at steady state (C_avg = AUC_0-t/dosing interval); C_max, maximum plasma concentration; T_max, time of maximum plasma concentration; T_1/2, terminal-phase half-life; CL/F, apparent total body clearance (CL/F = dose/AUC_0-∞); Vd/F, apparent volume of distribution.

Table 2 Posaconazole serum AUC/MIC target for aspergillosis and mucormycosis

Fungal culture		MIC of posaconazole (mg/L)	Target of AUC/MIC ratio	AUC0-12/MIC ratio	AUC0-24/MIC ratio
				300 mg q 12 hrs (day 1)		400 mg q 24 hrs (day 7)	400 mg q 24 hrs (day 14)	300 mg q 24 hrs (day 35)
Aspergillosis	A. fumigatus	0.01	300–500	815.15	1,630.30	7,618.43	7,746.44	4,923.02
	A. flavus	0.12	300–500	67.93	135.86	634.87	645.54	410.25
Mucormycosis	R. microsporus	0.25	>100	32.61	65.21	304.74	309.86	196.92
	L. corymbifera	0.25	>100	32.61	65.21	304.74	309.86	196.92

Abbreviations: MIC, minimum fungicidal inhibitory concentration; AUC/MIC ratio, area under concentration-time curve over minimum fungicidal inhibitory concentration (MIC); AUC_0-12, area under concentration-time curve from 0 to 12 hrs; AUC_0-24, area under concentration-time curve from 0 to 24 hrs.

Figure 2 Chest computed tomography of a patient with invasive pulmonary aspergillosis and mucormycosis. Before the start of posaconazole (A); day 35 after the start of posaconazole treatment (B); and, day 90 after the start of posaconazole treatment (C).