Oral administration pharmacokinetics

These systems have been used in many bioanalytical applications. A Prospekt system coupled with MS quantitated eserine N-oxide, a cholinesterase inhibitor, in human plasma for low level (4.5 mg) oral administration pharmacokinetic studies (Pruvost et al. 2000). After conditioning of the SPE cartridge (PLRP-S, Spark) with methanol (5 mL/min, 0.5 min) and water (5 mL/min, 0.5 min), a volume of 250 jj.L plasma plus internal standard was injected and washed (water, 1 mL/min, 3 min). The analytes were flushed out with 80 20 ammonium acetate (20 mM, pH 3.5 adjusted with formic acid) and acetonitrile (0.3 mL/min) and separated on a Zobax SB-CN column (150 x 2.1 mm inner diameter, 5 jim). A calibration range of 25 pg/mL to 12.5 ng/mL was achieved with a run time of 10.5 min. 

Figure 1.1 A schematic presentation of the fate of a drug in the body following oral administration. Pharmacokinetic processes are in blue, with the components of oral bioavailability in dark blue. Pharmacodynamic processes are in green, with the clinical effects in dark green.

The development of new antibiotics to combat resistance, and to provide easier oral administration and improved pharmacokinetics has been successful through synthetic modifications. This approach has been particularly rewarding in the area of P-lactams. The commercial importance of the P-lactams is evident from Table 3 which gives the market share of antibacterials. Fully 62% of the 1989 world antibacterial market belonged to the cephalosporin and penicillin P-lactams (20). 

Muzolimine (710), a 1-substituted 2-pyrazolin-5-one derivative, is a highly active diuretic, differing from the structures of other diuretics since it contains neither a sulfonamide nor a carboxyl group. It has a saluretic effect similar to furosemide and acts in the proximal tubule and in the medullary portion of the ascending limb of the loop of Henle. Pharmacokinetic studies in dogs, healthy volunteers and in patients with renal insufficiency show that the compound is readily absorbed after oral administration (B-80MI40406). 

Note Derivatization with this reagent sequence in combination with extraction and TLC separation is speciftc for amitriptyline and nortriptyline in the analysis of plasma furthermore its high sensitivity allows its employment in pharmacokinetic studies, e. g. after the oral administration of a single dose of 25 mg amitriptyline. 

Dopamine, a vasodilator, has been widely used for treatment of acute circulatory failure. However, since dopamine is rapidly metabolized when administered orally, its use has been limited to intravenous infusion. Murata et al., studied the bioavailability and the pharmacokinetics of orally administered dopamine (DA). The oral administration of DA to dogs resulted in an absolute bioavailability of approximately 3%. To minimize the extensive first-pass metabolism of DA, a dopamine prodrug, V-(/V-acetyl-l-mcLhionyl)-o,o-bis(cLhoxycarbonyl)dopamine (TA-870), was synthesized [28] (Fig. 6). Since DA is a substrate for both mono-... 

DS Davies. Pharmacokinetics of terbutaline after oral administration. Eur J Resp Dis Suppl 65 111-117, 1984. 

E Eichelbaum, HR Ochs, G Roberts, A Somogyi. Pharmacokinetics and metabolism of antipyrine after intravenous and oral administration. Arzneim-Forsch 32 575-578, 1982. 

Ohmoto, N. et al., MDR1 genotype-related pharmacokinetics of digoxin after single oral administration in healthy Japanese subjects, Pharm. Res. 2001, 18, 1400-1404. 

L. H., Karim, A., Drug, meal and formulation interactions influencing drug absorption after oral administration. Clinical implications, Clin. Pharmacokinet. 1999, 36, 233—254. 

Ohzawa et al [112] studied the absorption, distribution, and excretion of 14C miconazole in rats after a single administration. After the intravenous administration of 14C miconazole at a dose of 10 mg/kg to the male rats, the plasma concentration of radioactivity declined biophysically with half-lives of 0.76 h (a phase) and 10.32 h (/ phase). After oral administration of 14C miconazole at a dose of 1, 3, or 10 mg/kg to male rats, the plasma concentration of radioactivity reached the maximum level within 1.25 h, after dosing and the decline of radioactivity after the maximum level was similar to that after intravenous administration. At a dose of 30 mg/kg, the pharmacokinetic profile of radioactivity in the plasma was different from that at the lower doses. In the female rats, the plasma concentration of radioactivity declined more slowly than that in male rats. The tests were conducted on pregnant rats, lactating rats, bile-duct cumulated male rats. Enterohepatic circulation was observed. In the in situ experiment, 14C miconazole injected was observed from the duodenum, jejunum, and/or ileum, but not from the stomach. 

Dean et al. [93] used a high performance liquid chromatographic method for the simultaneous determination of primaquine and carboxyprimaquine in plasma with electrochemical detection. After the addition of the internal standard, plasma was deproteinized by the addition of acetonitrile. Nitrogen-dried supernatants, resuspended in mobile phase were analyzed on a C8 reversed-phase column. Limits of detection for primaquine and carboxyprimaquine were 2 and 5 ng/mL with quantitation limits of 5 and 20 ng/mL, respectively. The assay sensitivity and specificity are sufficient to permit quantitation of the drug in plasma for pharmacokinetics following low dose (30 mg, base) oral administration of primaquine, typically used in the treatment of malaria and P. carinii pneumonia. 

The pharmacokinetics of rifaximin after oral administration has been studied in healthy volunteers and patients with intestinal infections or IBD. The aim of these studies was to confirm the low, if any, systemic absorption of the drug metabolism and excretion data are scant. In all these investigations a sensitive high-pressure liquid chromatographic (HPLC) method was used to measure rifaximin in body fluids. 

Venturini AP Pharmacokinetics of L/105, a new rifamycin, in rats and dogs, after oral administration. Chemotherapy (Basel) 1983 29 1-3. 

Venturini AP L/105 Report on pharmacokinetics in rats, dogs after oral administration and adverse reactions. Chemioterapia (Florence) 1983 2(suppl 5) 162—163. 

Cellai L, Colosimo M, Marchi E, Venturini AP, Zanolo G Rifaximin (L/105), a new topical intestinal antibiotic Pharmacokinetic study after single oral administration of 3H-rifaximin to rats. Chemioterapia (Florence) 1984 3 373-377. 

Descombe JJ, Dubourg D, Picard M, Palaz-zini E Pharmacokinetic study of rifaximin after oral administration in healthy volunteers. Int J Clin Pharmacol Res 1994 14 51-56. 

The pharmacokinetic value that most reliably reflects the amount of drug reaching the target tissue after oral administration is the... 

Amlodipine — Ma et al.50 developed and validated a UPLC/MS/MS method for a pharmacokinetic study of amlodipine in human plasma after oral administration. Nimodipine 50 fig/mL in a mixture of methanol and water (50 50 v/v) served as the IS. Standard solutions of amlodipine were also prepared in a mixture of methanol and water (50 50 v/v). 

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