Effects of bile salts on the lovastatin pharmacokinetics following oral administration to rats

Figures & data

Table 1.  Intra- and inter-day precision and accuracy of the determination of lovastatin in plasma.

Concentration (ng/mL)	RSD (%)		Accuracy (%)
	Intra (n = 5)	Inter (n = 5)
0.039	3.39	7.41	108.12
0.3125	4.53	6.52	98.47
2.5	2.82	2.89	97.16
20	2.92	1.15	98.90

Figure 1.  Chromatograms of rat blank plasma (A), lovastatin (1.25 ng/mL, B), and IS (1 ng/mL, C).

Table 2.  Pharmacokinetic parameters of formulated lovastatin dosage forms.

	Tmax (h)	Cmax (ng/mL)	Half-life (h)	AUC0–10 (ng h/mL)	AUC0–∞ (ng h/mL)
Control	0.81 ± 0.28	0.32 ± 0.15	0.86 ± 0.14	0.33 ± 0.10	0.49 ± 0.16
NaDC19	0.45 ± 0.05	3.95 ± 1.25^a	1.21 ± 0.16	5.30 ± 1.86^a	5.56 ± 1.84^a
NaDC49	1.08 ± 0.35	1.46 ± 0.29	1.31 ± 0.51	2.96 ± 0.97	3.44 ± 1.11
NaDC69	0.54 ± 0.15	0.66 ± 0.16^b	1.06 ± 0.22	0.67 ± 0.13^b	0.90 ± 0.19^b
NaGC19	0.92 ± 0.15	1.31 ± 0.65	0.94 ± 0.13	2.29 ± 1.04	2.43 ± 0.99
NaGC49	0.71 ± 0.28	1.67 ± 0.96	1.21 ± 0.26	1.83 ± 0.76	2.14 ± 0.96
NaGC69	1.65 ± 1.09	0.54 ± 0.34^b	1.10 ± 0.55	0.95 ± 0.35	1.22 ± 0.52

Control, Mevastin^®; NaDC19, Lovastatin:NaDC (1:19); NaDC49, Lovastatin:NaDC (1:49); NaDC69, Lovastatin:NaDC(1:69); NaGC19, Lovastatin:NaGC (1:19); NaGC49, Lovastatin:NaGC (1:49); NaGC69, Lovastatin:NaGC(1:69). Data are expressed as the mean ± SE (n = 6).

^a p < 0.05 vs control.

^b p < 0.05 vs NaDC19.

Figure 2.  Mean pharmacokinetic profiles after administration of formulated lovastatin solid dispersions and commercial lovastatin tablet (Mevastin^®) at a dose of 2.5 mg/kg as lovastatin (Mean ± SE, n = 6). Ratio between drug and sodium deoxycholate is 1:19 (NaDC19), 1:49 (NaDC49), and 1:69 (NaDC69). Ratio between drug and sodium glycholate is 1:19 (NaGC19), 1:49 (NaGC49), and 1:69 (NaGC69).