Absorption, Distribution and Excretion
Piperyl butyl ether is a topical medication. A study assessing urinary accumulation of piperyl butyl ether within 7 days of topical application found that approximately 2% of the dose was absorbed through the skin. The scalp absorption rate was 8.3%. A human volunteer absorption study found that if piperyl butyl ether is absorbed, it is primarily excreted in the urine. The absorption of piperyl butyl ether in humans is extremely low. The volume of distribution has not been studied. The clearance rate of piperyl butyl ether has not been studied. Significant percutaneous absorption was not observed in experimental mammals. Radiometric distribution showed that in Madeira cockroaches, the highest concentrations of 14C-labeled piperyl butyl ether per unit weight were found in the brain and thoracic ganglia, foregut and hindgut, and Malpighian tubules of the kidneys. Piperyl butyl ether is poorly absorbed in the gastrointestinal tract. In two studies, 78% and 87% of the oral dose, respectively, were recovered from the feces of dogs. Small amounts of the drug absorbed from the gastrointestinal tract are rapidly excreted in the urine. Intratracheal administration prolongs the excretion time of metabolites in bile and urine, but even in this case, the residual amount in lung tissue is lower than that after intravenous administration. ...Oral administration of...(14)C-piperylbutyl ether 48 hours later...In mice, 76% of (14)C was excreted via exhaled air, 7% via urine, and 4% via feces...In rats, approximately 40% was excreted via exhaled air as (14)C-CO2 8 hours after intravenous administration...For more complete data on the absorption, distribution, and excretion of piperinylbutyl ethers (9 in total), please visit the HSDB record page.

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Metabolism/Metabolites
Piperylbutyl ethers are absorbed very little in humans. Their metabolism has not been studied.
[14C]-piperylbutyl ether (PBO) was administered to male and female rats by gavage at doses of 50 or 500 mg/kg body weight, respectively. In all cases, the radioactive material is rapidly excreted, with 87-99% present in excrement within 0-48 hours, and the majority of the dose (64.1-85.0%) excreted via feces. The metabolism of PBO is complex, with over 25 radioactive peaks detected by high-performance liquid chromatography (HPLC). The structures of 12 urinary metabolites and 4 fecal metabolites (including PBO) were identified using HPLC/tandem mass spectrometry (MS/MS) and nuclear magnetic resonance (NMR). Metabolism occurs at two sites: the methylenedioxy ring, which opens to form catechol, which can subsequently undergo methylation; and the 2-(2-butoxyethoxy)ethoxymethyl side chain, which undergoes successive oxidation to generate a series of alcohols and acids. The identified metabolites account for approximately 60% of the administered dose. In mice, the main metabolic pathway of piperonyl butyl ether involves the cleavage of methylenedioxyphenol residues and the excretion of the methylene carbon atom as CO2. The products in urine include many compounds without methylenedioxyphenyl residues, as well as small amounts of 6-propyl piperic acid and its glycine conjugate. In mammals (and insects), oxidative attack on the methylenedioxy carbon atom leads to the formation of dihydroxyphenyl compounds. Oxidative degradation of the side chain also occurs. In a metabolic study, a mixture of non-radioactively labeled (93.4% ai) and phenyl-labeled 14C-piperyl butyl ether (100% radiochemical purity) was administered by single gavage to four CRL:CD rats per group (per sex per dose) at doses of 50 or 500 mg/kg body weight. The primary route of excretion was feces; after 168 hours, the fecal radioactivity content in the low-dose group was 82.9–85.1% of the administered dose, and in the high-dose group it was 64.1–75.9%. Within 168 hours, the percentage of radioactive material excreted in urine was 11.1-14.4% in the low-dose group and 19.5-30.2% in the high-dose group. Most of the radioactive material in both dose groups was excreted in urine and fecal samples within 0-48 hours. The radiopharmaceutical uptake in the carcass was less than 0.5% in both the low-dose and high-dose groups. The total radiopharmaceutical recovery rate was between 97.4% and 99.6% in both dose groups. There were no significant differences in excretion patterns between the two dose groups or between different sexes within the same dose group. M1 and M3 were the main metabolites excreted in feces. M1 was identified as unmetabolized PBO, accounting for 15.6% to 23.9% of the administered dose. M3 was identified as PBO, with its methylenedioxy ring opening to form catechols, accounting for 17.4% to 19.7% of the administered dose. M2 and M4/M5 were also identified, but at lower levels in the high-dose group (4% to 6% of the administered radioactivity). Multiple radioactive peaks (approximately 20) were observed in urine samples, but none of the individual peaks exceeded 5% of the administered radioactivity. The major metabolite found in male urine was M14, at 3% of the administered dose. In female urine, the major metabolites identified were M6 and a mixture of M7/M8, at 5% and 9% of the administered dose, respectively. Although there was no significant difference in metabolite excretion between the two dose groups, metabolites M5, M8, M9, and M10 were predominantly present in female urine samples, while M14 was found only in male urine samples. Based on the metabolite identification results, the authors proposed three major reactions in PBO metabolism: 1) ring-opening of the methylenedioxy ring to generate catechol; 2) successive cleavage of the 2-(2-butoxyethoxy)ethoxymethyl side chain to generate a series of alcohols and acids; 3) conjugation of one of the phenolic hydroxyl groups with glucuronide, sulfate, or methoxy derivative.
Biological half-life
32 hours.
To determine the transdermal absorption of piperonyl butyl ether in humans, a commercial formulation containing (14C) piperonyl butyl ether (3.4 mCi/μM) was applied to the ventral forearm of six volunteers. This formulation contained 3.0% piperonyl butyl ether. The application study showed that the concentration of piperonyl butyl ether used in this study (75.8 μg/cm²) was consistent with the concentration used in actual applications. The forearm was thoroughly washed with soap and water 30 minutes after application (consistent with actual application recommendations). Transdermal absorption was determined by the cumulative excretion in urine after administration. After 7 days of urine accumulation, … 2.1 ± 0.6% of the piperonyl butyl ether dose was absorbed through the forearm skin. No radioactivity was detected in blood samples 1 hour after administration. The proportion of piperonyl butyl ether absorbed transdermally was calculated to be 8.3%. …The calculated 14C excretion half-life of piperonyl butyl ether was 32 hours.

Protein Binding
Piperidine is absorbed very little in humans. Protein binding has not been studied. Toxicity Data LC50 (Rat) > 5,900 mg/m³ Interactions Piperidine has been shown to inhibit drug metabolism… It competitively inhibits the N-demethylation of ethylmorphine and the O-demethylation of p-nitrobenzyl ether… …In mouse studies, it has been shown to significantly increase the toxicity of Freon and griseofulvin, and vice versa. For some sulfur-containing organophosphorus insecticides that require metabolic activation… it antagonizes normal insecticidal efficacy. Pyrethroid synergists, such as piperin… are effective against DDT,… against carbamates,… against diazinon, trichlorfon, and other phosphates,… but they antagonize malathion… For more complete data on interactions with piperin (11 in total), please visit the HSDB records page.

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Non-human toxicity values
Oral LD50 in rats: 11.5 g/kg
Acute oral LD50 in male rats: 4570 mg/kg
Acute oral LD50 in female rats: 7220 mg/kg
Dermal LD50 in rats: >7950 mg/kg
For more non-human toxicity values (complete data) for piperonyl butyl ether (11 in total), please visit the HSDB record page.

Therapeutic Uses
Piperyl butyl ether itself has no known therapeutic uses. ...Pyrethroid formulations containing piperyl butyl ether can be used as liceicides to control human lice (Pediculus humanus humanus), head lice (P. humanus capitus), and pubic lice (Pthirus pubis)... Pharmacodynamics Piperyl butyl ether does not affect the human mixed-function oxidase system. In small human volunteer trials, commonly used doses of piperyl butyl ether had no effect on humans.

C19H30O5

338.44

338.209

51-03-6

Piperonyl butoxide-d9;1329834-53-8

5794

Colorless to light yellow ointment

1.1±0.1 g/cm3

396.2±0.0 °C at 760 mmHg

165.3±27.2 °C

0.0±0.8 mmHg at 25°C

1.503

4.23

0

5

13

24

312

0

CCCC1=C(COCCOCCOCCCC)C=C2OCOC2=C1

FIPWRIJSWJWJAI-UHFFFAOYSA-N

InChI=1S/C19H30O5/c1-3-5-7-20-8-9-21-10-11-22-14-17-13-19-18(23-15-24-19)12-16(17)6-4-2/h12-13H,3-11,14-15H2,1-2H3

5-[2-(2-butoxyethoxy)ethoxymethyl]-6-propyl-1,3-benzodioxole

NSC-8401; NSC 8401; Piperonyl butoxide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Ethanol : ~100 mg/mL (~295.47 mM)
DMSO : ~100 mg/mL (~295.47 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.39 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.39 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (7.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)