1) ¹⁴C-L-DOPSを経口投与したマウス，ラット，イヌおよびアカゲザルの尿中に，未変化体とともに，主要代謝体として3-OM-DOPSおよびPA，VAとこれらの抱合体が，さらに，ラットおよびアカゲザルではHCの抱合体が同定された．
2) 血清，肝臓および尿中には未変化体が最も多く存在し，尿中に投与量の10～20%が排泄された．尿中には代謝体として3-OM-DOPSが6～15%，PAおよびVAの抱合体がそれぞれ10～20%および2～11%排泄され，ラットおよびアカゲザルではHCの抱合体も微量検出された．
3) ¹⁴C-L-DOPSを経口投与した各種実験動物の血清および尿中のNEおよびNEの代謝体は，投与前と比べて明らかに増加したが，いずれの実験動物においても，¹⁴C-L-DOPS投与後の尿中のNEおよびNEの代謝体の排泄量の合計は投与量の1%以下であった．
4) ¹⁴C-L-DOPS投与後のラットの腎臓中NE濃度は，アカゲザルより約6倍高かった．

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GC/MSによるカルバサイクリン誘導体，CS-570のイヌ血漿中定量法を確立した．本法はODSおよびSiミニカラムによるclean-up法とメチル-DMiPS誘導体化を用いることにより，1ng/mlのCS-570を定量できた．
CS-570をイヌに静注および持続静注し，その体内動態を解析した．その結果，CS-570の血漿中半減期は約10分と極めて短く，速やかに循環血流から消失することが明らかになった．また持続静注を行うと，投与開始後15分で定常状態の95%に到達することが判明した．

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The absorption and excretion of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazole difumarate (KB-2413) were studied in rats and guinea pigs after oral administration of KB-2413-¹⁴C. Maximum plasma levels (C_max) appeared at 0.25 and 0.5 h after dosing in rats and guinea pigs, respectively. In rats, both C_max and the area under the plasma concentration-time curve (AUC) increased proportionally to the administered dose up to 8mg/kg.
The radioactivity excreted into the urine and the AUC after oral dosing in rats and guinea pigs were close to those after intravenous dosing, and the orally administered radioactivity was almost completely excreted into the bile and urine in the bile-duct-cannulated rats. Thus, it was suggested that KB-2413 was nearly completely absorbed from the intestinal tract of rats and guinea pigs.
The percentages of the radioactivity excreted in feces were 65.3 and 58.9 % of the dose within 96 h after oral administration of KB-2413-¹⁴C in rats and guinea pigs, respectively.
The radioactivity excreted into the bile was about 90 % of the dose within 24 h after oral dosing in bile-duct-cannulated rats. The enterohepatic circulation in rats was suggested, since a considerable amount of the radioactivity was absorbed in the rat which was administered intraduodenally with the bile collected from other rats administered with KB-2413-¹⁴C orally.

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The distribution of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazole difumarate (KB-2413) was studied in rats after single and multiple oral administrations of KB-2413-¹⁴C.
The radioactivity was high in the intestine, liver, pancreas and kidney, and low in the central nervous system and in the fat after single oral administration to fasted rats.
The steady-state during multiple oral administration, was reached after the 7 th dose as shown by a constant values of the tissue-to-plasma concentration ratio and AUC_0-24h.
The radioactivity excreted into both urine and feces was about 98 % within 4 d after the 14 th administration. At this time, the concentration in most tissues was lower than that at 24 h after the 1 st administration.

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The transfer of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazole difumarate (KB-2413) to the fetus and milk was studied in pregnant and nursing rats, respectively, after oral administration of KB-2413-¹⁴C.
The maximum level of the radioactivity in each tissue of fetal rats was reached at 2 h after dosing. At that time, the concentration in the fetus homogenate was comparable to that in the maternal plasma. The radioactivity in the fetal liver and intestine was relatively high, suggesting that the radioactivity was transfered to bile in fetuses as well as in male rats.
The radioactivity was transfered to milk after oral administration to nursing rats. Milk/plasma concentration ratios were less than 1 within 8 h. The elimination half-life of the radioactivity in milk was about 16h.

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The interaction of acetohexamide with probenecid was investigated in rabbits.
1. Probenecid significantly enhanced the hypoglycemic activity of acetohexamide after its oral administration. In addition, probenecid markedly increased the plasma concentrations of acetohexamide and its pharmacologically active metabolite, hydroxyhexamide.
2. Probenecid significantly decreased the urinary excretion of hydroxyhexamide after oral administration of acetohexamide, but caused no change in the urinary excretion of the parent compound. Probenecid non-competitively inhibited the metabolic reduction of acetohexamide by the liver cytosol.
3. Probenecid itself had little effect on the in vitro binding of acetohexamide or (−)-hydroxyhexamide to the serum, but a mutual displacement of serum protein binding was observed between acetohexamide and (−)-hydroxyhexamide.
Evidence obtained in this study suggests that the interaction of acetohexamide with probenecid is a complex process.

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1．ラットに[¹⁴C] GTNを頸静脈内持続単回投与したとき，血漿中放射活性は投与終了時点で最高値を示し，投与中に定常状態に達することはなかった．これは連続投与の場合でも同様であった．単回投与後の血中からの減衰は二相性を示し，半減期はα相で2.59時間，β相で28.11時間であった．
2．連続投与後の血漿中放射活性の半減期は単回投与と比較すると，α相ではほとんど変わらなかったが，β相は約2倍になった．これは連続投与によって生成した半減期の長い代謝物が長時間体内を循環しているためと考えられる．
3．単回投与後，72時間までに尿，呼気，糞中に合計約73%が排泄されたが，残り27%は体内に残留した．連続投与後72時間の尿，呼気，糞中排泄は，おのおの38.3%，27.8%，6.9%，合計約73%であり，単回投与の場合と同様な結果であった．
4．投与後24時間までの尿中代謝物は，単回投与，連続投与ともGTNの脱ニトロ体(GDN，GMN)とそのグルクロン酸抱合体，グリセリンおよび未知成分であった．グリセリンは恐らくクレブスサイクルを経て炭酸ガスとして呼気中に排泄されるものと考えられる．
5．連続投与期間中，尿中代謝物の割合にあまり変化がみられなかったことから，体内の代謝酵素系は連続投与を行っても影響を受けないものと推測され，実験の結果，本薬物の代謝に重要な役割を演じている肝ミクロソーム中のUDP-グルクロニルトランスフェラーゼについてこのことが確かめられた．
6．体内の組織・臓器においても，血漿中濃度の場合と同様，未変化体の割合が多い投与および投与終了直後は減衰が速く，代謝の進んだ投与終了後は時間の経過とともに減衰速度も緩慢となった．
7．持続注入中は標的組織の1つである動脈，静脈へ比較的高濃度に分布することから，臨床治療上の有効性が示唆された．
8．各種組織・臓器中の濃度を単回投与と連続投与とで比較したところ，連続投与の場合に臓器蓄積性が認められた．これは血漿中濃度の場合と同様，減衰速度の遅い代謝物が連投することにより連日蓄積して行き，その結果，蓄積が認められるようになったものと推測される．

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Enantiomers of many drugs show differences in pharmacological activities and in metabolisms. Since such drugs are often used as racemic mixtures, it is important to determine the amounts of each enantiomer in biological fluids in order to optimize therapy and to avoid undesirable side effects. Recently, chromatographic methods have been developed for the separation of enantiomeric compounds. In principle, enantiomers are resolved in two ways.
(1) Derivatization to diastereomers with a chiral reagent followed by chromatographic separation on a nonchiral column (Indirect method).
(2) Use of a chiral mobile phase or stationary phase which forms diastereomeric complexes with the enantiomers in a column. Because of difference in their stabilities, the two enantiomers are eluted from the column at different rates (Direct method).
In this review, liquid chromatographic separation of enantiomeric drugs is described.

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