## 3 Pharmacokinetics of Tanshinones
### The Pharmacokine (PK) Characteristics of Single Administered Agents or as Mixtures
Second, the drug-concentration time courses of tanshinones fit well into two-compartment or multiple-compartment models after _i.v._ administration in rats, rabbits and pigs. There is usually a very fast component with a half-life of under 10 min (Table 2) and a slower component with half-life ranging 1-3 h. Pharmacokine interactions can occur between tanshinones and polyphenolic extracts of _Salvia mitlorrhiza_ Bunge after intravenous administration, as seen in the study of [PERSON] _et al._[97] in rats by PK of the marker compound TIIA and salvianolic acid B (Sal B) as a marker for polyphenolic extract. The authors documented an increase of AUC of about 2-fold in both the low and medium dose groups (2 and 4 mg/kg) for TIIA and Sal B, while there was at least a 14- and 5-fold significant increase (\(p<0.01\)) for TIIA and Sal B in the high dose groups, respectively, which was due to a significant (\(p<0.01\)) reduction in total plasma clearance. The peak plasma concentrations (\(C_{\rm 5 min}\)) of TIIA were significantly increased by including the polyphenolic extract in the emulsion (up to 28-fold) \begin{table}
\begin{tabular}{l l l l l l l l l} \hline \hline \multirow{2}{*}{**Species**} & \multicolumn{2}{l}{**Administered**} & \multirow{2}{*}{**Route**} & \multirow{2}{*}{**Dose**} & \multirow{2}{*}{**PK for**} & \multirow{2}{*}{\(C_{\rm A+B}\), \(C_{\rm max}\) or \(C_{\rm t}\) (\(\mu\)M)**} & \multirow{2}{*}{**t\({}_{1/2B}\) (h)**} & \multirow{2}{*}{**t\({}_{1/2T}\) (h)**} & \multirow{2}{*}{**References**} \\  & \multicolumn{2}{l}{**(marker compound)**} & & & & & & & \\ \hline Rat & Tanshinones Mixture & _p.o._ & 18 & TIIA & 0.06 (@_t_max 4h) & & & [104] \\  & (TIIA) & & _p.o._ & 18 & CT & 0.027 (@_t_max 4 h) & & \\  & Tanshinones Mixture (CT) & & & & & & & \\ Rat & Tanshinones Mixture & _p.o._ & 4.1 & TIIA & 0.009 (@_t_max 0.54 h) & & 2.07 & [105] \\  & (TIIA) & & & & & & & \\  & Tanshinones Mixture (CT) & _p.o._ & 1.91 & CT & 0.002 (@_t_max 0.42 h) & & 1.13 \\  & Tanshinones Mixture (TI) & _p.o._ & 1.1 & TI & 0.006 (@_t_max 0.42 h) & & 3.00 \\  & Tanshinones Mixture & _p.o._ & 1.91 & DH-TI & 0.012 (@_t_max 0.79 h) & & 1.69 \\  & (DH-TI) & & & & & & \\ Rat & Tanshinones Mixture & _p.o._ & 5.79 & TIIA & 0.076 (@_t_max 0.61 h) & 0.40 & 3.70 & [106] \\  & (TIIA) & & & & & & \\  & Tanshinones Mixture (CT) & _p.o._ & 9.82 & CT & 0.145 (@_t_max 0.86 h) & 0.69 & 2.81 \\  & Tanshinones Mixture (TI) & _p.o._ & 3.9 & TI & 0.198 (@_t_max 0.60 h) & 0.94 & 4.72 \\  & Tanshinones Mixture & _p.o._ & 3.58 & DH-TI & 0.041(@_t_max 0.74 h) & 0.54 & 3.65 \\  & (DH-TI) & & & & & & \\ Rat & Danshen tanshinone & _p.o._ & 20 & TIIA & 0.057 (@_t_max 6.67 h) & & 7.04 & [107] \\  & extract (TIIA) in CMC & & & & & & \\  & 0.5\% & & & & & & \\  & tanshinone extract + & _p.o._ & 20 & TIIA & 0.060 (@_t_max 4.35 h) & & 5.86 \\  & salvianolic acid B extract & & & & & & \\  & tanshinone extract + & _p.o._ & 20 & TIIA & 0.054 (@_t_max 4.33 h) & & 6.90 \\  & notoginseng extract & & & & & & \\  & Tanshinone extract + & _p.o._ & 20 & TIIA & 0.066 (@_t_max 2.00 h) & 0.032 & 6.28 \\  & borneol (Bingpian) & & & & & & \\  & All extracts combined & _p.o._ & 20 & TIIA & 0.075 (@_t_max 3.67 h) & 0.041 & 6.02 \\ \hline \hline \end{tabular} \(t_{1/2B}\): initial phase elimination half-life; \(t_{1/2P}\): terminal elimination phase half-life; \(C_{\rm A}+C_{\rm B}\): Extrapolated initial concentrations of two compartments; \(C_{\rm max}\): maximal/peak concentration; _i.v. i.p. i. m._ and _p.o._: intravenous, intraperitoneal, intramuscular and oral administration, respectively.  
\end{table} 
Table 2: _Cont._(Table 2). However, such interactions did not appear to be as dramatic when examined by oral delivery as shown in the study of [PERSON] _et al._[107], although some shifts in the absorption of TIIA and its transfer from central compartment to the peripheral compartment were noted. Third, _in vivo_ metabolism or biotransformation of some tanshinones, especially CT to TIIA, has been noted in a number of species (pig, rat) [100; 101; 102].