Bioavailability and Pharmacokinetics of Natural Volatile Terpenes in Animals and Humans

Abstract

Herbal medicinal products containing natural volatiles are used in the treatment of gastrointestinal diseases, pain, colds and bronchitis. Many pharmacological studies report a wide variety of in vitro effects, with anti-inflammatory and antimicrobial activities investigated most frequently. In comparison, relatively few studies on the bioavailability and pharmacokinetics have been carried out. Thus, the relevance of the in vitro activity to the therapeutic effects found in individual studies or documented in textbooks of phytotherapy is still not established. Further studies with essential oils and their single compounds providing supporting evidence of efficacy and demonstrating systemic availability are necessary. Such data could also be important in the context of safety.

Key words

Terpenes - volatiles - herbal medicinal products - bioavailability - pharmacokinetics

References

• 1 Teuscher  E.. Biogene Arzneimittel. 5th ed. Stuttgart:; Wissenschaftliche Verlagsgesellschaft mbH, 1997
• 2 Malo  J L,, Boulet  L P,, Dewitte  J D,, Cartier  A,, L'Archeveque  J,, Cote  J,, Bedard  G,, Boucher  F,, Champagne  F,, Tessier  G.. Quality of life of subjects with occupational asthma.  Journal of Allergy and Clinical Immunology. 1993;;  91 1121-7
• 3 Grimm  G.. Antiobstruktive Wirksamkeit von Cineol bei Atemwegserkrankungen.  Therapiewoche. 1987;;  37 4306-11
• 4 Dorow  P.. Welchen Einfluß hat Cineol auf die mukoziliäre Clearance? Chronisch-obstruktive Bronchitis.  Therapiewoche. 1989;;  39 2652-4
• 5 Federspil  P,, Wulkow  R,, Zimmermann  T.. Wirkung von Myrtol standardisiert bei der Therapie der akuten Sinusitis - Ergebnisse einer doppelblinden, randomisierten Multicenterstudie gegen Placebo.  Laryngo-Rhino-Otologie. 1997;;  76 23-7
• 6 Ernst  E,, März  R W,, Sieder  C.. A controlled multi-centre study of herbal versus secretolytic drugs for acute bronchitis.  Phytomedicine. 1997;;  4 287-93
• 7 Morgenstern  E.. Die antiphlogistische Wirkung von Bronchipret und seiner Komponenten im Rattenpfoten-Ödem-Modell. In: März R, Editor Bronchitis. Neue Erkenntnisse zu Wirkungen und Wirksamkeit von Arzneipflanzen. Basel, Freiburg, Paris:; Karger, 1998: 1-8
• 8 Liu  J H,, Chen  G H,, Yeh  H Z,, Huang  C K,, Poon  S K.. Enteric-coated peppermint-oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial.  Journal of Gastroenterology. 1997;;  32 765-8
• 9 Pittler  M H,, Ernst  E.. Peppermint oil for irritable bowel syndrome: a critical review and metaanalysis.  American Journal of Gastroenterology. 1998;;  93 1131-5
• 10 May  B,, Kuntz  H D,, Kieser  M,, Kohler  S.. Efficacy of a fixed peppermint oil/caraway oil combination in non-ulcer dyspepsia.  Arzneimittelforschung. 1996;;  46 1149-53
• 11 Göbel  H,, Fresenius  J,, Heinze  A,, Dworschak  M,, Soyka  D.. Effektivität von Oleum menthae piperitae und von Paracetamol in der Therapie des Kopfschmerzes vom Spannungstyp.  Nervenarzt. 1996;;  67 672-81
• 12 Loew  D.. Ätherische Öle in der Behandlung der Erkältungskrankheiten. In: Tyrrell DAJ, Editor Erkältungskrankheiten. Ein Lehrbuch für die Praxis. Stuttgart, Jena, New York:; Fischer, 1996: 100-8
• 13 Göckeritz  D,, Weuffen  W,, Höppe  H.. Terpene und Terpenderivate vom Carvon- und Camphertyp - ihre antimikrobiellen und verminoxen Eigenschaften.  Pharmazie. 1974;;  29 339-43
• 14 Maruzella  J C,, Liguori  L.. The in vitro antifungal activity of essential oils.  Journal of the American Pharmaceutical Association. 1958;;  47 250-4
• 15 Janssen  A M,, Chin  N LJ,, Schefer  J JC,, Baerheim Svendsen  A.. Screening for antimicrobial activity of some essential oils by the agar overlay technique.  Pharmaceutisch Weekblad. 1986;;  8 289-92
• 16 Pattnaik  S,, Subramanyam  V R,, Kole  C.. Antibacterial and antifungal activity of ten essential oils in vitro. .  Microbios. 1996;;  86 237-46
• 17 Römmelt  H,, Zuber  A,, Dirnagl  K,, Drexel  H.. Zur Resorption von Terpenen aus Badezusätzen.  Münchner Medizinische Wochenschrift. 1974;;  116 537-40
• 18 Schäfer  R,, Schäfer  W.. Die perkutane Resorption verschiedener Terpene - Menthol, Campher, Limonen, Isobornylacetat, alpha-Pinen - aus Badezusätzen.  Arzneimittelforschung. 1982;;  32 56-8
• 19 Schuster  O,, Haag  F,, Priester  H.. Transdermale Absorption von Terpenen aus den etherischen Ölen der Pinimenthol-S-Salbe.  Die Medizinische Welt. 1986;;  37 100-2
• 20 Diliberto  J J,, Usha  G,, Birnbaum  L S.. Disposition of citral in male Fischer rats.  Drug Metabolism and Disposition. 1988;;  16 721-7
• 21 Diliberto  J J,, Srinivas  P,, Overstreet  D,, Usha  G,, Burka  L T,, Birnbaum  L S.. Metabolism of citral, an alpha,beta-unsaturated aldehyde, in male F344 rats.  Drug Metabolism and Disposition. 1990;;  18 866-75
• 22 Bounds  S V,, Caldwell  J.. Pathways of metabolism of [1′-¹⁴C]-trans-anethole in the rat and mouse.  Drug Metabolism and Disposition. 1996;;  24 717-24
• 23 Römmelt  H,, Schnitzer  W,, Swoboda  M,, Senn  E.. Pharmakokinetik ätherischer Öle nach Inhalation mit einer terpenhaltigen Salbe.  Zeitschrift für Phytotherapie. 1988;;  9 14-6
• 24 Römmelt  H,, Drexel  H,, Dirnagl  K.. Wirkstoffaufnahme aus pflanzlichen Badezusätzen.  Die Heilkunst. 1978;;  91 249-54
• 25 Levin  J O,, Eriksson  K,, Falk  A,, Lof  A.. Renal elimination of verbenols in man following experimental alpha-pinene inhalation exposure.  International Journal of Occupational and Environmental Health. 1992;;  63 571-3
• 26 Austgulen  L,, Solheim  E,, Scheline  R.. Metabolism in rats of p-cymene derivatives: carvacrol and thymol.  Pharmacology and Toxicology. 1987;;  61 98-102
• 27 Takada  M,, Agata  I,, Sakamoto  M,, Yagi  N,, Hayashi  N.. On the metabolic detoxification of thymol in rabbit and man.  Journal of Toxicological Sciences. 1979;;  4 341-50
• 28 Sangster  S A,, Caldwell  J,, Smith  R L.. Metabolism of anethole. II. Influence of dose size on the route of metabolism of trans-anethole in the rat and mouse.  Food and Chemical Toxicology. 1984;;  22 707-13
• 29 Sangster  S A,, Caldwell  J,, Smith  R L,, Farmer  P B.. Metabolism of anethole. I. Pathways of metabolism in the rat and mouse.  Food and Chemical Toxicology. 1984;;  22 695-706
• 30 Sangster  S A,, Caldwell  J,, Hutt  A J,, Anthony  A,, Smith  R L.. The metabolic disposition of [methoxy-¹⁴C]-labelled trans-anethole, estragole and p-propylanisole in human volunteers.  Xenobiotica. 1987;;  17 1223-32
• 31 Sutton  D,, Sangster  S,, Caldwell  J.. Dose-dependent variation in the disposition of eugenol in the rat.  Biochemical Pharmacology. 1985;;  34 465-6
• 32 Somerville  K W,, Richmond  C R,, Bell  G D.. Delayed release peppermint oil capsules (Colpermin) for the spastic colon syndrome: a pharmacokinetic study.  British Journal of Clinical Pharmacology. 1984;;  18 638-40
• 33 Kaffenberger  R M,, Doyle  M J.. Determination of menthol and menthol glucuronide in human urine by gas chromatography using an enzyme-sensitive internal standard and flame ionization detection.  Journal of Chromatography. 1990;;  527 59-66
• 34 Bell  G,, Henry  D,, Richmond  C.. A specific g.l.c. assay for menthol in urine.  British Journal of Clinical Pharmacology. 1981;;  12 281
• 35 Yamaguchi  T,, Caldwell  J,, Farmer  P B.. Metabolic fate of [³H]-L-menthol in the rat.  Drug Metabolism and Disposition. 1994;;  22 616-24
• 36 Mans  M,, Pentz  R.. Pharmacokinetics of menthol in the rat.  Nauyn-Schmiedebergs Archives of Pharmacology. 1987;;  335 R6
• 37 Kleinschmidt  J,, Römmelt  H,, Zuber  A.. The pharmacokinetics of the bronchosecretolytic ozothin after intravenous injection.  International Journal of Clinical Pharmacology, Therapy, and Toxicology. 1985;;  23 200-3
• 38 Falk  A,, Hagberg  M.. Uptake, distribution and elimination of alpha-pinene in man after exposure by inhalation.  Scandinavian Journal of Work, Environment and Health. 1990;;  16 372-8
• 39 Jager  W,, Nasel  B,, Nasel  C,, Binder  R,, Stimpfl  T,, Vycudilik  W,, Buchbauer  G.. Pharmacokinetic studies of the fragrance compound 1,8-cineol in humans during inhalation.  Chemical Senses. 1996;;  21 477-80
• 40 Kovar  K,, Gropper  B,, Friess  D,, Ammon  H.. Blood levels of 1,8-cineole and locomotor activity of mice after inhalation and oral administration of rosemary oil.  Planta Medica. 1987;;  53 315-8
• 41 Zimmermann  T,, Seiberling  M,, Thomann  P,, Karabelnik  D.. Untersuchungen zur relativen Bioverfügbarkeit und zur Pharmakokinetik von Myrtol standardisiert.  Arzneim.-Forsch./Drug Res.. 1995;;  45 1198-201
• 42 Parke  D,, Rahman  Q,, Walker  R.. The absorption, distribution and excretion of linalool in the rat.  Biochemical Society Transactions. 1974;;  2 612-8
• 43 Caldwell  J,, Sutton  J D.. Influence of dose size on the disposition of trans-[methoxy-¹⁴C]-anethole in human volunteers.  Food and Chemical Toxicology. 1988;;  26 87-91